Effects of an oral water load and intravenous administration of isotonic glucose, hypertonic saline, mannitol and furosemide on the release of atrial natriuretic peptide in men

The effects of an oral water load and iv administration of isotonic glucose, hypertonic saline, mannitol and furosemide on release of human atrial natriuretic peptide (hANP) were examined in normal subjects to determine the main factors causing its release. In addition, the influence of age on hANP secretion was investigated. The mean plasma hANP level in normal subjects, 0-89 years old, was 20.6 +/- 1.1 ng/l (mean +/- SEM) and showed age-related change. The plasma hANP level did not change significantly after a water load or infusion of isotonic glucose, but rose significantly from 11.4 +/- 1.4 to 15.6 +/- 3.2 ng/l after infusion of hypertonic saline and from 10.9 +/- 1.6 to 17.8 +/- 4.1 ng/l after infusion of 20% mannitol in parallel with the increase in plasma volume. The plasma hANP level decreased from 17.3 +/- 2.5 to 9.0 +/- 2.5 ng/l after injection of 40 mg of furosemide. A positive correlation was found between change in the plasma hANP level and percent change in the plasma volume (P less than 0.001) on these treatments. The response of plasma hANP to hypertonic saline infusion was greater in older than in young men. These results indicate that 1) the secretion of hANP shows an age-related change and 2) increase in the circulating plasma volume is an important factor regulating hANP secretion.     

The relationship of saline-induced changes in vasopressin secretion to basal and corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol secretion in man

To investigate the effect of endogenous arginine vasopressin (AVP) on ACTH secretion, normal subjects were given infusions of either hypertonic saline (HS) or isotonic saline (NS) combined with human corticotropin-releasing hormone (CRH) or placebo. Basal plasma AVP was 2.3 +/- 0.3 (+/- SE) pg/ml, did not change with NS treatment, and rose to 5.4 +/- 0.6 pg/ml during HS infusion (P less than 0.01). Both basal and CRH-stimulated plasma ACTH and cortisol concentrations increased during HS infusion. Peak plasma ACTH and cortisol levels were 11.4 +/- 1.5 pg/ml and 8.6 +/- 0.8 micrograms/dl, respectively, during the HS (plus placebo) infusion. During the NS (plus placebo) infusion, plasma ACTH and cortisol gradually declined to 6.8 +/- 0.5 pg/ml and 2.6 +/- 0.4 micrograms/dl. The timing of the rise in ACTH during the HS infusion paralleled the rise in AVP. When an iv dose of 1 microgram/kg CRH was administered during the saline infusions, peak plasma ACTH and cortisol levels were 27.7 +/- 6.3 pg/ml and 17.5 +/- 1.0 micrograms/dl, respectively, during the HS infusion and 15.6 +/- 1.7 pg/ml and 13.4 +/- 1.2 micrograms/dl during the NS infusion. When the areas under the hormone response curves were compared, CRH stimulated ACTH and cortisol secretion to a greater extent than did HS (P less than 0.05). The hormonal stimulation due to combined CRH and hypertonic saline was greater than that attributable to either factor alone (P less than 0.025), but was not different than the sum of the effects of the individual factors. These results indicate that increases in endogenous AVP produced by HS are associated with increases in both basal and CRH-stimulated ACTH and cortisol release. The effect of HS appears to be additive to but not consistently synergistic with the effect of CRH.     

Effect of various states of hydration on plasma ADH and renin in man.

To investigate the interaction between antidiuretic hormone (ADH) and renin-angiotensin system, plasma ADH and plasma renin activity (PRA) were determined in normal subjects (n = 10) under various hydrated states. Four experimental conditions, i.e., water loading, infusion of hypertonic saline, acute dehydration induced by furosemide and postural changes, were chosen. 1. Upright posture decreased plasma volume by 9.5 +/- 0.9% without significant changes in plasma osmolality. PRA increased from 5.2 +/- 0.7 to 8.3 +/- 0.8 ng/ml. However, plasma ADH did not change significantly (1.9 +/- 0.3 to 1.8 +/- 0.2 muU/ml). 2.When furosemide was administered intravenously under this condition, both plasma ADH and PRA increased to 3.1 +/- 0.5 muU/ml and 15.5 +/- 1.6 ng/ml with 11.2 +/- 1.1% decrease in plasma volume. Plasma osmolality did not change significantly. 3.Water load resulted in a decrease in plasma osmolality from 282.6 +/- 0.9 to 278.6 +/- 1.2 mOsm/kg without significant change in plasma volume. Significant decrease in plasma ADH level from 2.6 "/- 0.4 to 0.6 "/- 0.1 muU/ml was found, but PRA (7.8 +/- 1.1 ng/ml) did not change (6.3 +/- 1.0 ng/ml). 4. Hypertonic saline infusion brought about an increase in plasma osmolality to 290.1 +/- 0.8 mOsm/kg with simultaneous increase in plasma volume by 6.7 +/- 1.3%. Plasma ADH level also increased to 2.4 +/- 0.3 muU/ml, while PRA decreased to 4.2 +/- 0.3 mg/nl. Accordingly, significant correlation between changes in PRA and plasma ADH level, was not observed. We suggest that plasma osmolality is the dominant variable in regulating plasma ADH level, but in the presence of a sufficient degree of hypovolemia, the osmotic domination was overcome. On the other hand, PRA was strongly influenced by changes in effective blood volume other than changes in plasma osmolality.     

Plasma levels and cardiovascular, endocrine, and excretory effects of atrial natriuretic peptide during different sodium intakes in man

Endogenous plasma concentrations of human atrial natriuretic peptide (alpha hANP) as well as effects of synthetic alpha hANP on some cardiovascular, endocrine, and renal excretory parameters were investigated in 10 normal subjects during sodium (Na+) intakes of 17, 140, and 310 mmol/day, respectively. Plasma hANP was slightly but not significantly higher after 5 days of normal or high sodium intake than after 5 days of low sodium intake [54 +/- 13, 46 +/- 8, and 37 +/- 5 (mean +/- SEM) pg/ml, respectively]. alpha hANP infused at 0.1 microgram/kg X min during all Na+ intakes produced a similar fall in diastolic blood pressure (P less than 0.001) and rise in heart rate (P less than 0.001), a comparable percent increase in plasma norepinephrine (P less than 0.001), and a reduction in plasma cortisol and aldosterone (P less than 0.01-0.001) despite raised renin activity (P less than 0.05-0.001) and unchanged plasma electrolytes. alpha hANP-induced plasma volume contraction, diuresis, and natriuresis were greater during high than low Na+ intake (P less than 0.01-0.001). Therefore, in normal man different Na+ intakes are accompanied by marked modifications in renal excretory responsiveness to alpha hANP. Regardless of sodium intake, alpha hANP can promote BP reduction and hemoconcentration, elicit reflex (?) sympathetic activation, and depress basal circulating aldosterone and cortisol levels in the face of an activated renin system.     

Influence of infused hypertonic saline on the response to insulin-induced hypoglycemia in man

We studied the influence of a hypertonic saline infusion on the counterregulatory response to insulin-induced hypoglycemia in nine normal men. When given hypertonic saline, the men had less hypoglycemia in response to insulin, both acutely and in the recovery phase (P less than 0.01), and released 34% more glucagon (P less than 0.05) than when they were water loaded. The total integrated ACTH, cortisol, epinephrine, norepinephrine, and GH responses to hypoglycemia were similar after saline and water loading. After the saline load, the mean plasma vasopressin level rose from 11.0 +/- 2.2 (+/- SEM) to 20.9 +/- 2.9 pg/mL in response to insulin-induced hypoglycemia. In contrast, after the water load, vasopressin levels were undetectable (less than 2 pg/mL) and they increased only to 2.6 +/- 0.4 pg/mL with hypoglycemia. There was a significant positive correlation between basal plasma vasopressin and nadir glucose concentrations and a significant negative correlation between basal plasma vasopressin and the integrated fall in glucose after insulin administration (P less than 0.01 and P less than 0.025, respectively). The difference in the glycemic response to insulin may be related to the high vasopressin levels after saline loading, which could, either directly and/or through enhanced glucagon release, increase hepatic glucose production and thus limit the hypoglycemic response to insulin.     

Changes in plasma atrial natriuretic polypeptide concentration during head-out water immersion and saline infusion in normal men

The physiological mechanism regulating secretion of human atrial natriuretic polypeptide (hANP) was examined by measuring plasma hANP by a specific radioimmunoassay during head-out total body water immersion (WI) and saline infusion in normal men. Seven healthy men were immersed in water for 1 hour, 6 normal men and women were given an infusion of 1 liter of normal saline over 1 hour and 8 normal men were given a similar infusion over 2 hours. During WI, the urinary volume (UV) and urinary Na excretion (UNaV) increased significantly, and the plasma hANP level increased significantly from 246 +/- 12 (mean +/- SE) pg/ml to 392 +/- 32 pg/ml after 35 +/- 5 min, but returned to the basal level after 90 min. The increase in hANP level was correlated with an increased UNaV between 30 to 60 min during WI. The plasma norepinephrine, renin activity, aldosterone and cortisol levels also decreased during WI. Saline infusion caused variable increases in the hANP level: the mean peak values of hANP and times of the peaks from the start of saline infusion were respectively 305 +/- 30 pg/ml after 30 +/- 3 min of infusion at a rate of 1L/1 hr and 285 +/- 25 pg/ml after 69 +/- 15 min of infusion at a rate of 1L/2 hrs. The time of the peak of plasma hANP during infusion at 1L/2 hrs was significantly longer than the peaks for WI or an infusion of saline at 1L/1 hr. Moreover, the peak hANP level was significantly smaller during either condition of saline infusion than during water immersion. These results indicate that i) acute central hypervolemia caused by WI increases hANP secretion, and this increase may participate in natriuresis during WI, and ii) saline infusion causes an increase in plasma hANP of variable magnitude, the increase being more rapid for a more rapid infusion of saline. This suggests that hANP is released into the circulation by acute volume expansion and plays a physiologically important role in maintaining blood volume homeostasis in man.     

Plasma human atrial natriuretic peptide, endothelin-1, aldosterone and plasma-renin activity in pregnancy-induced hypertension.

OBJECTIVE: To determine the relationship between endothelin-1 (ET-1), human atrial natriuretic peptide (hANP), plasma-renin activity (PRA) and 24-h urinary excretion of aldosterone (U-Ald) in pregnancy-induced hypertension (PIH). DESIGN AND METHODS: Plasma hANP (pg/ml), ET-1 (pg/ml), PRA (ng/ml per h) and U-Ald (microg/24 h) were measured and 24 h ambulatory mean arterial pressure (MAP) was monitored in 178 normotensive subjects (NT) and 79 gravidas with PIH at the 8th, 18th, 23rd, 28th, 32nd and 36th weeks. RESULTS: The PIH group had higher MAP than the NT group from the 23rd week (91.64 +/- 8.76 versus 83.48 +/- 4.36 mmHg, P< 0.01) until the end of the pregnancy. ET-1 levels (pg/ml) in both groups were identical at the beginning of pregnancy and different in the 23rd week [(NT versus PIH) (35.11 +/- 17.42 and 40.2 +/- 19.51, respectively, P < 0.05)] and the 36th week (37.36 +/- 18.07 and 42.7 +/- 16.43, P< 0.05). hANP levels (pg/ml) in the NT group decreased insignificantly from the 8th till the 32nd week, then increased to 101.94 +/- 17.4 in the 36th (P< 0.001 versus any other week). In the PIH group, hANP increased from 104.8 +/- 26.8 pg/ml at the 8th week to 161.3 +/- 28.6 pg/ml at the 36th week (P< 0.0001). hANP correlated with MAP in the NT group (r = 0.252, P< 0.0005) but not the PIH group. U-Ald in the NT group increased from 23.52 +/- 6.83 microg/24 h at the 8th week to 54.07 +/- 19.62 microg/24 h at the 36th week (P < 0.0001) and in the PIH group it increased from 27.90 +/- 11.6 to 53.66 +/- 20.4 microg/24 h (P< 0.0001). In the PIH group, PRA was lower compared with the NT group from the 8th (2.99 +/- 1.26 versus 4.10 +/- 1.82 ng/ml per h, P< 0.05) until the 36th week (3.34 +/- 2.16 versus 4.46 +/- 2.13 ng/ml per h). In the forced multiple regression analysis model with hANP as a dependent variable, a value of P< 0.003 was found with PRA, U-Ald and MAP, which indicates an interaction between the two vasoactive and homeostatic systems: the renin-angiotensin-aldosterone system and hANP. CONCLUSIONS: In PIH, elevated hANP might be important as a counterbalance to the presence of the active vasopressors and sodium retention. By inhibiting renin release, enhancing the transcapillary fluid migration and with its action as vasodilator, it acts as a corrective factor of the imbalance between the contracted circulating fluid volume and the vasoconstricted vascular bed.     

Clinical assessment of posterior pituitary function by direct measurement of plasma vasopressin levels during hypertonic saline infusion

Clinical usefulness of a radioimmunoassay of plasma arginine vasopressin concentration (AVP) during hypertonic saline infusion for the assessment of posterior pituitary function was studied in comparison with the conventional water deprivation test. Infusion of 5% saline at a rate of 0.05 ml/kg/min for 120 min in 15 normal subjects induced an elevation of plasma osmolality (Posm) from 290.3 +/- 0.7 to 307.5 +/- 2.1 mOsm/kg with a resultant increase in AVP from 2.4 +/- 0.4 to 9.9 +/- 2.2 pg/ml. During the infusion, a highly significant correlation between AVP and Posm was observed with a regression line expressed as AVP = 0.40 (Posm - 283.0). In 22 polyuric patients, on the other hand, the infusion induced a marked elevation of Posm from 302.6 +/- 2.5 to 321.3 +/- 2.9 mOsm/kg, but caused a slight (less than 5.8 pg/ml) or no increase in AVP from the basal levels (0.5 +/- 0.1 pg/ml). A conventional water deprivation test was carried out in ten patients with neurogenic diabetes insipidus, including one who had coincidental nephrogenic diabetes insipidus. As would be expected, urine osmolality (Uosm) did not rise beyond Posm in seven of them. However, two of three other patients, who had a complete lack of AVP response to the hypertonic saline, were able to concentrate their urine with a maximal Uosm/Posm of 1.3 and 1.1 respectively. The concurrent decrease in creatinine clearance to 49 and 57% of the initial values, respectively, indicated that a marked reduction in glomerular filtration rate due to severe dehydration was responsible for the unexpected concentration of urine in the patients with totally impaired AVP secretion. Based on these results, we conclude that the direct measurement of AVP during hypertonic saline infusion is an essential procedure for the accurate evaluation of posterior pituitary function.     

Trials for simplified hypertonic saline test

Hypertonic saline test is indispensable for the evaluation of posterior pituitary function. However the test is not simple, including water loading, urine sampling and at least 45 min of hypertonic saline infusion, mostly because the test relies on urinary osmolality as an index of ADH secretion. The object of this study is try to simplify the test by directly measuring plasma ADH concentration before and after 10 min of hypertonic saline infusion. Intravenous infusion of hypertonic saline (5% NaCl, 0.24 ml/kg/min, for 10 min) was performed on normal subjects, patients with diabetes insipidus and patients with renal failure under chronic hemodialysis. Venous blood samples were obtained seriously including just before and after 10 min of the infusion. ADH was extracted from plasma using Sep-Pak C18 column and assayed by specific RIA. Minimum sensitivity of the assay was 0.25 pg/ml. The hypertonic saline infusion resulted in an increase of plasma osmolality by about 8 mOsm/kg H2O and plasma sodium concentration by 4 mEq/l. Plasma ADH increased from 0.77 +/- 0.09 to 3.42 +/- 0.73 pg/ml (m +/- SE, n = 8, p less than 0.01) in normal subjects of ad lib. water drinking and from 0.55 +/- 0.33 to 2.34 +/- 0.33 (m +/- SE, n = 4, p less than 0.05) in water loaded normal subjects (20 ml/kg of water, 60 min before hypertonic saline infusion).(ABSTRACT TRUNCATED AT 250 WORDS)     

Depressor effects and release of atrial natriuretic peptide during norepinephrine or angiotensin II infusion in man

Alpha-human atrial natriuretic peptide (alpha hANP) is the major circulating form of ANP in man. The potential of synthetic alpha hANP to antagonize the pressor action of norepinephrine (NE) or angiotensin II (AII) and a possible influence of NE or AII pressor infusions on circulating immunoreactive ANP (irANP) were investigated in 14 normal young subjects. After titration of doses to increase mean blood pressure by about 20 mm Hg, NE or AII was infused at a constant rate for 110 min. Mean blood pressure (BP) was similar during NE and AII infusions [109 +/- 4 (+/- SEM) and 108 +/- 3 mm Hg, respectively]. However, synthetic alpha hANP injected in stepwise increasing doses of 10, 40, and 75 micrograms caused significantly greater (P less than 0.001) BP reductions during NE infusion. alpha hANP lowered BP progressively from 147/91 +/- 5/3 to 136/70 +/- 5/3 mm Hg during NE infusion (P less than 0.001) and only minimally from 133/96 +/- 3/3 to 132/89 +/- 4/4 during AII infusion. Heart rate was elevated more (P less than 0.01) after alpha hANP injection during NE infusion. Endogenous plasma irANP increased significantly after 20 min of NE or AII pressor infusion (P less than 0.01 and P less than 0.05, respectively); this rise was more pronounced (P less than 0.05) during NE (from 25 +/- 2 to 80 +/- 20 pg/ml) than during AII (from 21 +/- 3 to 31 +/- 3 pg/ml) infusion. These findings suggest that alpha hANP interacted preferentially with noradrenergic as compared to angiotensinergic BP control. Conversely, for a given rise in BP, NE elicited a greater rise in circulating irANP.     

Changes in plasma copeptin, the c-terminal portion of arginine vasopressin during water deprivation and excess in healthy subjects

CONTEXT: The measurement of arginine vasopressin (AVP) is often cumbersome because it is unstable with a short half-life time. AVP is derived from a larger precursor peptide along with the more stable peptide copeptin. Copeptin is the C-terminal part of provasopressin and has been shown to be a useful tool to indicate AVP concentration in critically ill patients. OBJECTIVE: The objective of the study was to evaluate the clinical usefulness of copeptin as a new marker in disordered states of blood volume and plasma osmolality. DESIGN AND SETTING: This was a prospective observational study in a university hospital. PARTICIPANTS AND MAIN OUTCOME MEASURES: Three techniques with respective control studies were used in 24 healthy adults to produce changes in plasma osmolality and/or volume: 1) a 28-h water deprivation, 2) a 17-h hypertonic saline infusion combined with thirsting, and 3) a hypotonic saline infusion with iv desmopressin administration during free water intake. RESULTS: Water deprivation produced a weight loss of 1.7 kg, an increase in plasma osmolality to 294.8 +/- 4.3 mosmol/kg, and an increase of copeptin from 4.6 +/- 1.7 pmol/liter to 9.2 +/- 5.2 pmol/liter (P < 0.0001). During hypertonic saline infusion and thirsting with a raise of plasma osmolality to 296.1 +/- 3.4 mosmol/kg, copeptin increased from 4.9 +/- 3.0 pmol/liter to 19.9 +/- 4.8 pmol/liter (P < 0.0001). Conversely, during hypotonic saline infusion, plasma osmolality decreased to 271.3 +/- 4.1 mosmol/kg, and copeptin decreased from 6.2 +/- 2.4 pmol/liter to 2.4 +/- 2.1 pmol/liter (P < 0.01). CONCLUSION: Copeptin shows identical changes during disordered water states as previously shown for AVP. It might be a reliable marker of AVP secretion and substitute for the measurement of circulating AVP levels in clinical routine.     

High plasma concentrations of human atrial natriuretic polypeptide in aged men

To examine the effect of age on the secretion and action of human atrial natriuretic polypeptide (hANP), we compared plasma atrial natriuretic polypeptide and cGMP concentrations in 19 normal young (24-28 yr old) and 31 elderly (64-91 yr old) men. The mean basal plasma hANP level was 25 +/- 5 (+/- SEM) pg/ml in the young men and 120 +/- 22 pg/ml in the elderly men (P less than 0.01). The molecular size of plasma hANP in an aged man was similar to that of alpha hANP. The responses of plasma hANP and cGMP concentrations to an iv infusion of 500 ml 0.15 M NaCl also was compared. Mean plasma hANP concentrations increased significantly in both groups, and the response in the elderly men was exaggerated compared to that in the young men. However, the increases in plasma cGMP concentrations during NaCl loading were similar in both groups. We conclude that 1) the plasma hANP concentrations in healthy elderly men are higher than those in young men, and 2) the higher plasma hANP concentrations may be a compensatory response to reduced hANP activation of its receptors.     

Osmoregulation of vasopressin secretion in the insulin-withdrawn streptozotocin-treated diabetic rat

To investigate whether hyperglycaemic ketoacidotic diabetic rats continue to osmoregulate the secretion of arginine vasopressin (AVP), male Wistar rats were injected with streptozotocin (150 mg/kg body weight). Rats rendered diabetic were maintained on protamine-zinc insulin (PZI) for 11 days (insulin-treated rats; n = 35), after which PZI was withdrawn for 72 h in half the rats (insulin-withdrawn rats). Insulin-withdrawn and -treated rats were divided into two groups; one was injected i.p. with distilled water (20 ml/kg) and the other with hypertonic saline (500 mmol NaCl/l; 20 ml/kg), and killed 30 min after injection. Insulin-withdrawn rats (water loaded and osmotically stimulated) were hyperglycaemic (16.5 +/- 0.8 and 16.5 +/- 0.9 mmol glucose/l respectively) and ketotic (2077 +/- 664 and 1474 +/- 170 mumol acetoacetate/l respectively). Insulin-treated rats were euglycaemic and non-ketotic. Osmotic manipulation caused similar changes in plasma sodium in both insulin-withdrawn and -treated rats. Plasma AVP was low in the water-loaded rats (0.6 +/- 0.1 and 4.5 +/- 0.9 pmol/l in the insulin-treated and -withdrawn rats respectively) and increased in rats injected with hypertonic saline (1.2 +/- 1.8 and 35.2 +/- 17.9 pmol/l respectively). There was no evidence of hypotension and hypovolaemia in any group of rats. Linear regression analysis defined the functions: plasma AVP = 2.56 (plasma Na-141), r = +0.63, P less than 0.01 for hyperglycaemic ketotic rats; plasma AVP = 0.83 (plasma Na-146), r = +0.78, P less than 0.001 for insulin-treated animals. The slopes and abscissal intercepts were significantly (P less than 0.05) different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of posture and ageing on circulating atrial natriuretic peptide levels in man

Possible influences of posture or age on plasma immunoreactive atrial natriuretic peptide (irANP) levels and potential correlates were assessed in 12 young (age +/- s.e.m. 24 +/- 1 year) and 12 elderly (63 +/- 8 year) healthy subjects on a liberal sodium intake. The groups did not differ significantly in their basal 24-h urinary sodium excretion (210 +/- 23 versus 180 +/- 15 mmol/l). However, plasma irANP was five- to ninefold higher in the elderly (P less than 0.05-0.01). Plasma irANP averaged 167 +/- 31 and 24 +/- 3 pg/ml in the elderly and young, respectively, during recumbency, fell (P less than 0.05) to 101 +/- 21 and 11 +/- 1 pg/ml, respectively, with upright posture, and rose (P less than 0.01) to 250 +/- 51 and 50 +/- 9 pg/ml, respectively, after intravenous (i.v.) loading with 0.9% saline (2.14 l in 3 h). Supine blood pressure (BP) and plasma norepinephrine tended to be higher while renin and aldosterone levels were lower (P less than 0.01) in the elderly; the three latter variables rose (P less than 0.001) with upright posture. These findings demonstrate that in normal humans, circulating irANP levels vary with posture and ageing. These changes may have potential physiological relevance and should be considered when interpreting plasma irANP levels in pathological conditions.     

Role of endogenous nociceptin in the regulation of arginine vasopressin release in conscious rats

The effects of central administration of the opioid-like peptide nociceptin (also known as orphanin FQ) were investigated on the secretion of arginine vasopressin (AVP) in response to dehydration and hyperosmolar or hypovolemic stimulation in conscious rats. Intracerebroventricular (i.c.v.) administration of nociceptin suppressed plasma AVP concentration in a dose-dependent manner (0.1-10 microg/rat) in dehydrated rats, and the maximum effect was obtained 10 min after the administration (dehydration with 10 microg/rat nociceptin, 3.11 +/- 0.27 pg/ml vs. control, 10.32 +/- 0.96 pg/ml). The plasma AVP increase in response to either hyperosmolality [i.p. injection of hypertonic saline (HS) (600 mosml/kg)] or hypovolemia [i.p. injection of polyethylene glycol (PEG)] was also significantly blunted when nociceptin was injected i.c.v. (HS with 10 microg/rat nociceptin, 1.16 +/- 0.09 pg/ml vs. control, 1.82 +/- 0.30 pg/ml; PEG with 10 microg/rat nociceptin, 0.91 +/- 0.16 pg/ml vs. control, 2.41 +/- 0.26 pg/ml). Pretreatment with a selective opioid kappa-receptor antagonist, nor-binaltorphimine (1 microg/ rat, i.c.v.) or naloxone (2.5 mg/rat, s.c. injection) did not reverse the inhibitory effects of nociceptin on AVP release. Moreover, when plasma AVP was suppressed by acute water loading, immunoneutralization of endogenous nociceptin by antinociceptin-antiserum i.c.v. significantly reversed the suppression (0.57 +/- 0.12 pg/ml vs. control, 0.25 +/- 0.04 pg/ml). These results suggest that central nociceptin is physiologically involved in the control of AVP release through an inhibitory action.     

Increase in plasma concentrations of atrial natriuretic peptide during infusion of hypertonic saline in conscious newborn calves

Plasma concentrations of atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma concentrations of aldosterone, urine flow rate and sodium and potassium excretion were studied in two groups of four conscious 3-day-old male calves, infused with hypertonic saline or vehicle. Hypertonic saline infusion (20 mmol NaCl/kg body weight) was accompanied by a progressive rise in plasma concentrations of ANP (from 16.5 +/- 0.2 pmol/l at time 0 to 29.3 +/- 3.0 pmol/l at 30 min; P less than 0.05) and by a gradual decrease in PRA (from 1.61 +/- 0.23 nmol angiotensin I/l per h at time 0 to 0.54 +/- 15 nmol angiotensin I/l per h at 90 min; P less than 0.05); there was no change in the plasma concentration of aldosterone. Within the first 2 h of the 24-h urine collection period there was a marked rise in urine flow rate and sodium excretion in treated calves when compared with control animals (66.0 +/- 8.3 vs 15.9 +/- 1.2 ml/kg body weight per 2 h (P less than 0.05) and 6.7 +/- 1.3 vs 0.4 +/- 0.02 mmol/kg body weight per 2 h (P less than 0.01) respectively). During the following 22 h, urinary water and sodium excretion remained at significantly high levels. Thus, in the conscious newborn calf, changes in plasma ANP levels and urinary water and sodium excretion during hypertonic saline infusion are compatible with the hypothesis that endogenous ANP participates, at least in part, in the immediate diuretic and natriuretic renal response induced by the sodium overload.     

Significance of oxytocin to disorders of fluid and electrolyte metabolism in patients with essential hypertension

A possible involvement of oxytocin (OT) has been indicated in regulation of water and electrolyte metabolism, based on findings that the secretion of OT is increased by either water deprivation or sodium loading. However, to date, no informations have yet been obtained about the role of OT in hypertension. The present study was therefore undertaken to elucidate the role of OT for abnormalities of fluid and electrolyte metabolism in essential hypertension (EH) in comparison with normotensive subjects (NT). The major results were as follows. Plasma level of OT was 3.7 +/- 2.1 pg/ml (mean +/- SD) in EH, not significantly higher than that in NT (3.2 +/- 1.7 pg/ml). Plasma OT in low-renin EH (4.8 +/- 2.5 pg/ml) was significantly different from that in high-renin EH (2.9 +/- 1.4 pg/ml, p less than 0.05) and NT (p less than 0.05), but not in normal-renin EH (3.8 +/- 2.0 pg/ml). Plasma OT was inversely correlated with plasma renin activity (PRA) in EH (r = -0.384, p less than 0.01), but not in NT (r = 0.102). No significant correlation was found between plasma OT and plasma aldosterone concentration (PAC), plasma concentration of antidiuretic hormone (ADH), serum sodium and potassium, blood pressure and renal function in either EH or NT. I.m. injection of OT (0.04 IU/kg) increased significantly urinary excretions of sodium and potassium in EH and NT. However, the increment in sodium excretion was greater in low-renin EH than that in normal-renin EH (0.05 less than p less than 0.10), high-renin EH (p less than 0.05) and NT (p less than 0.05). PRA, PAC and ADH were significantly decreased after OT injection, but blood pressure, serum sodium and potassium were not altered in both EH and NT. I.v. administration of OT (0.1 approximately 0.2 IU/min) suppressed angiotensin II-induced increase of PAC and elevation of blood pressure in both EH and NT. The decrease in PAC by the OT administration was the greatest in low-renin EH. The reduction of blood pressure was significantly greater in EH than in NT (p less than 0.05). I.v. administration of hypertonic saline (5%) resulted in a significant increase of plasma OT in EH and NT, and the increment in OT was the greatest in low-renin EH. Serum sodium concentration was increased by the infusion, positively correlated with plasma OT in both EH (r = 0.458, p less than 0.05) and NT (r = 0.830, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Increases in plasma digitalis-like factor activity during insulin-induced hypoglycemia

Digitalis-like factor (DLF) appears to be widely distributed throughout the body, and has been specifically localized to the mammalian hypothalamus. In this study we monitored the DLF response to insulin-induced hypoglycemia in 11 normal males. Hypoglycemia was associated with a significant increase in serum DLF activity over basal values (40 +/- 5 pg digoxin Eq/ml, mean +/- SEM) at 60 min (83 +/- 8 pg digoxin Eq/ml) and 90 min (86 +/- 10 pg digoxin Eq/ml) following insulin administration (p less than 0.01). We measured the DLF response to insulin-induced hypoglycemia in other men after infusion of hypertonic saline (n = 8) or after oral water-loading (n = 8). Saline infusion (0.06 ml 5% saline/kg BW/min for 120 min prior to insulin infusion) or water loading (20 ml/kg BW over 60 min completed 30 min before insulin infusion) alone significantly increased serum DLF (saline: 21 +/- 5 to 60 +/- 18 pg digoxin Eq/ml, p less than 0.05; water: 18 +/- 11 to 49 +/- 15 digoxin Eq/ml, p less than 0.05). DLF activity was further significantly increased within each group 60 and 90 min after administration of insulin. In the group infused with hypertonic saline, insulin caused increases of serum DLF from 60 +/- 18 at time 0 to 170 +/- 17 pg digoxin Eq/ml at peak (p less than 0.01). Similarly, in the oral water-loaded group serum DLF increased from 49 +/- 15 at time 0 to 127 +/- 24 pg digoxin Eq/ml at peak (p less than 0.01) after they received insulin.2=     

Simultaneous radioimmunoassay for plasma arginine-vasopressin and oxytocin using DEAE Sephadex A 25 extraction

A sensitive and specific radioimmunoassay method for simultaneous measurement of plasma arginine vasopressin (AVP) and oxytocin (OT) has been developed utilizing an extraction technique on DEAE Sephadex A25. This procedure resulted in mean recoveries of 70.7% (AVP) and 65.4% (OT) in the peptide range of 5 to 100 pg/4 ml. The sensitivity of the assay is 0.5 pg/tube for AVP and 2 pg/tube for OT. The lower limit of detection for plasma extracts was 1.2 pg AVP/ml and 5 pg OT/ml plasma. Employing this method in normal human non smokers and ad libitum fluid the basal levels (mean +/- SE) of plasma AVP are 3.5 +/- 0.2 pg/ml in males and 4.6 +/- 0.4 pg/ml in females and the basal concentrations of plasma OT are 5.1 +/- 0.3 pg/ml in males and 5.4 +/- 0.3 pg/ml in females. Dehydration and water loading produced significant changes in plasma AVP and OT concentrations and a significant correlation exists between plasma AVP and plasma (r = 0.96, p less than 0.001) and urinary (r = 0.84, p less than 0.01) osmolality, but not between plasma OT concentrations and plasma (r = 0.11, NS) and urinary (r = 0.27, NS) osmolality. These results suggest that a wide range of physiological and pathophysiological changes in plasma AVP and OT can be simultaneously measured by the extraction procedure and the radioimmunoassay described.     

Baroreceptor influences on oxytocin and vasopressin secretion

The objective of these studies was to investigate the role of arterial baroreceptors in the control of neurohypophyseal secretion. The effect of sinoaortic denervation on basal and osmotic-induced release of oxytocin and vasopressin and on blood pressure was determined. Hypertonic or isotonic saline was infused intravenously into sham-operated or denervated rats 3 days after surgery. Plasma oxytocin and vasopressin were measured at 5 and 15 minutes after the infusion. The control levels of oxytocin were increased in the denervated rats, but vasopressin levels were not significantly altered. The vasopressin and oxytocin responses to hypertonic saline were greater after baroreceptor denervation. Plasma oxytocin was increased from 4.7 +/- 0.9 to 72.2 +/- 8.7 pg/ml in the denervated rats and from 1.8 +/- 0.3 to 39.9 +/- 6.7 pg/ml in the sham-operated control group at 5 minutes after the infusion (p less than 0.01). The plasma vasopressin response to hypertonic saline was 7.1 +/- 0.6 pg/ml in the sham-operated versus 11.1 +/- 1.6 pg/ml in the denervated rats (p less than 0.05). There was no difference between sham-operated and denervated rats in the effect of hypertonic saline on plasma sodium and hematocrit. Mean arterial blood pressure was increased after sinoaortic denervation (116.3 +/- 4.2 mm Hg in the sham-operated vs. 138.2 +/- 8.3 mm Hg in the denervated rats, p less than 0.05); however, there was no difference in the pressor response to hypertonic saline. These results show that the baroreceptor system influences the secretion of both oxytocin and vasopressin, with effects on basal secretion as well as the response to an osmotic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)