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.     

Effects of sodium intake, furosemide, and infusion of atrial natriuretic peptide on the urinary and metabolic clearances of arginine vasopressin in normal subjects

Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) have important influences on water and electrolyte metabolism, and studies on the interactions between these hormones may have important implications. We have investigated the effects of sodium intake, furosemide, and infusion of ANP on the urinary and metabolic (nonurinary) clearances of AVP in hydrated normal subjects. On a high sodium diet there was an increase in urine volume, sodium excretion, osmolal clearance, plasma ANP concentration, and urinary clearance and fractional excretion of AVP, with a decrease in PRA. The infusion of furosemide increased urine volume, sodium excretion, osmolal clearance, and PRA, but decreased circulating ANP levels and urinary clearance and fractional excretion of AVP. Since there was a positive correlation between circulating ANP and urinary clearance of AVP in these experiments, we infused human alpha ANP in physiological amounts and found increases in the urinary and metabolic (nonurinary) clearances of AVP. The changes in urinary clearance of AVP in all three experiments occurred even in relation to creatinine clearance. These observations demonstrate that urinary clearance of AVP does not correlate with urine volume, sodium or solute excretion, or PRA. The observations support a physiological role for ANP in modulating the renal action of AVP, probably at the level of the renal tubules, and indicate a need for caution when using plasma or urinary AVP as an indicator of AVP release from the neurohypophysis.     

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.     

Effect of a hypertonic saline load on plasma concentrations of atrial natriuretic peptide in fetal calves and their dams

Plasma concentrations of atrial natriuretic peptide (ANP) were studied in eight adult non-pregnant cows and in two groups of six chronically catheterized bovine fetuses and their mothers in the eighth month of pregnancy. The first group of fetuses was used for studying the effect of an acute i.v. sodium load (240 mmol NaCl/fetus) on fetal ANP; the second group acted as controls. The mean basal ANP levels in the third-trimester bovine fetus were three to four times higher than maternal values (39.5 +/- 5.5 and 9.4 +/- 0.6 pmol/l respectively; P less than 0.01). Basal maternal plasma ANP levels were twice as high in pregnant cows in the third trimester of pregnancy than in non-pregnant cows (9.4 +/- 0.6 and 4.3 +/- 0.7 pmol/l respectively; P less than 0.05). In response to an i.v. hypertonic saline injection, fetal plasma ANP levels increased significantly (P less than 0.01) to a maximum of 86.7 +/- 17.6 pmol/l 10 min after the injection, and returned to baseline within 60 min after the treatment; during the 20 min following the i.v. sodium load, fetal plasma ANP correlated significantly with fetal plasma sodium concentrations (r = 0.96; n = 12) and with fetal plasma osmolality (r = 0.94; n = 12). No significant changes in maternal ANP values were observed in the two groups of animals. These results suggest that ANP secretion is stimulated during pregnancy in cows, and that, in the bovine fetus, a hypertonic sodium load appears to be a potent stimulus for ANP release.     

Pressure dependence of atrial natriuretic peptide during norepinephrine infusion in humans

The relative contribution of increased blood pressure (BP) or norepinephrine (NE), or both, to the stimulatory effect of an NE pressor infusion on circulating immunoreactive atrial natriuretic peptide (ANP) was evaluated in 10 healthy young men. They were studied during an infusion of NE, which was applied initially alone and then in combination with sodium nitroprusside. NE infusion rate was increased in four 30-minute intervals to a final dose of 200 ng/kg body weight per minute, leading to 12-fold higher plasma NE levels than were seen during control conditions. This increased mean BP (from a mean basal value of 94 +/- 3 to 119 +/- 4 [SEM] mm Hg; p less than 0.001) and plasma immunoreactive ANP (from 50 +/- 7 to 112 +/- 17 pg/ml; p less than 0.001), whereas heart rate decreased (p less than 0.001). The NE infusion was continued at the highest dose and an additional infusion of sodium nitroprusside was started to titrate mean BP in 30-minute intervals down to control values; a mean sodium nitroprusside dose of 0.95 micrograms/kg/min restored mean BP to 93 +/- 4 mm Hg (p less than 0.001), decreased plasma immunoreactive ANP to basal values (51 +/- 4 pg/ml; p less than 0.001), increased heart rate (p less than 0.001), and left plasma levels of NE largely unchanged. Plasma protein and hematocrit rose about 5 to 6% (p less than 0.001) during the NE infusion and then decreased about 3 to 4% (p less than 0.001 and p less than 0.01) when sodium nitroprusside was added.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dopamine infusion on the release of atrial natriuretic factor

We evaluated the effects of dopamine infusion (1.5 micrograms/Kg/min for 60 min) on secretion of atrial natriuretic factor before raised diuresis could affect extracellular fluid volume and hence peptide release. We investigated ten healthy subjects without cardiovascular, renal or endocrine disease and ten patients with congestive heart failure (New York Heart Association Classes III and IV). The study protocol required four 30 minute clearance periods: 1st basal, 2nd during placebo, 3rd and 4th during dopamine infusion. We measured diuresis, natriuresis, glomerular filtration rate, blood pressure, heart rate, central venous pressure and plasma concentrations of atrial natriuretic factor, noradrenaline, renin activity, aldosterone and antidiuretic hormone. Blood samples were drawn at the midpoint of each clearance period after measuring blood pressure, heart rate and central venous pressure. Atrial natriuretic factor was determined by radioimmunoassay after chromatographic extraction, noradrenaline was measured fluorometrically while plasma renin activity, aldosterone and antidiuretic hormone concentrations were obtained by radioimmunoassay. During dopamine infusion plasma atrial natriuretic factor plasma levels were significantly raised in healthy subjects while high basal values of the peptide in patients with congestive heart failure were significantly reduced; this trend was also evident for noradrenaline levels in both groups. Plasma renin activity, aldosterone and antidiuretic hormone values remained unchanged in healthy subjects, but plasma renin activity and aldosterone levels dropped significantly in congestive heart failure patients. Diuresis, natriuresis and glomerular filtration rate were significantly increased while blood pressure, heart rate and central venous pressure remained unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma atrial natriuretic peptide in vasopressin deficiency: the effects of acute water deprivation in rats.

Plasma concentrations of atrial natriuretic peptide (ANP) and other renally active hormones were measured in Long-Evans (LE) rats and vasopressin-deficient Brattleboro rats with diabetes insipidus (DI) in conditions of water repletion and deprivation, and in DI rats following chronic vasopressin replacement. In water-replete rats, vasopressin deficiency was associated with elevated circulating ANP and angiotensin II (AII) concentrations, while plasma adrenal steroid concentrations were depressed by comparison with LE rats. These differences were fully reversed after 7 days of vasopressin replacement in DI rats to restore normal water turnover. Water deprivation for 4 h had little effect on plasma tonicity or hormone profile in LE rats. In contrast, however, the unreplaced fluid loss during 4-h water deprivation in the DI rat was associated with a marked increase in plasma tonicity evident within 30 min. Plasma ANP concentrations fell substantially to levels below those in LE rats, coincident with a rise in adrenal steroid levels and independent of any clear change in AII. These changes in circulating ANP concentration were directly correlated with changes in plasma Na+ concentration, osmolality and tissue water content in the DI rats, underlining the importance of body fluid status in modulating the secretion of ANP. These data clearly show that plasma ANP concentration is increased in vasopressin deficiency, but emphasize the sensitivity of circulating hormone levels in vasopressin-deficient animals to acute changes in the state of hydration, underscoring the complex and labile interaction between body fluid and hormonal factors involved in the control of ANP secretion.     

In vitro evidence for an inhibitory effect of atrial natriuretic peptide on vasopressin release

The effect of Arg-atriopeptin III (ANP) on basal and stimulated (angiotensin II, acetylcholine and KCl depolarization) arginine vasopressin (AVP) release was characterized in the intact hypothalamo-neurohypophysial explant (HNS) and in isolated neurointermediate pituitary lobes (NIL). In initial experiments using 15-min incubation periods, ANP 10(-10) and 10(-9) M slightly inhibited basal AVP release in both NIL and HNS after a delay of at least 15 min. The most effective ANP concentration was 10(-10) M, and the inhibitory effect on AVP release was more marked in HNS (-52 +/- 5% of control compared to -29 +/- 8% for NIL). However, ANP 10(-10) M did not significantly attenuate KCl- or AII (10(-5) M)-stimulated AVP release from HNS after 15 min of exposure. When the incubation periods were increased to 30 min ANP 10(-10) and 10(-9) M significantly decreased AII-stimulated (10(-5) M) AVP release in a dose-dependent manner (p less than 0.05; p less than 0.01, respectively). The same concentrations of ANP did not significantly depress ACH-stimulated (10(-5) M) AVP release (p less than 0.1 for both concentrations). In summary, ANP generally inhibits AVP release in vitro by a slowly activated mechanism which appears to be specific for certain physiological stimuli. Although the site(s) of action cannot be absolutely localized to the ventral hypothalamus and/or the neurohypophysis, an effect in the hypothalamus seems very likely.     

Effects of atrial natriuretic peptide on the coronary arterial vasculature in humans

The effects of the synthetic 28-amino-acid alpha-human atrial natriuretic peptide (ANP) on the proximal coronary arteries and coronary blood flow were evaluated in 17 patients. Proximal coronary dimension was quantitated by digital angiography, and coronary flow was quantitated with 3F Doppler flow catheters. ANP, when given as a 2.5-micrograms/kg bolus in the left ventricle, caused sustained significant proximal coronary dilations from 3.49 +/- 0.57 to 4.09 +/- 0.76 mm, lasting more than 30 minutes. The proximal coronary diameter did not increase further after intracoronary injection of 0.3 mg nitroglycerin (4.08 +/- 0.79 mm). Coronary flow (resistance coronary dilation) was not significantly increased at 5 minutes after ANP (87 +/- 55 to 102 +/- 54 vol flow units), indicating that the proximal coronary dilations were not flow dependent. The persistent proximal coronary dilations were associated with minor and transient decreases in aortic pressure and left ventricular end-diastolic pressure and with minor and transient increases in heart rate, cardiac output, and left ventricular contractility. Plasma ANP level increased significantly by more than sixfold from 39.8 +/- 8.8 to 245.8 +/- 168.5 pg/ml. The time course of proximal coronary dilations was related more closely to the time course of increase in plasma cyclic guanosine monophosphate than that of plasma ANP. This study demonstrates that bolus injection of ANP (2.5 micrograms/kg), an endogenous vasodilator, caused marked sustained preferential proximal coronary dilations and brief minor changes in cardiac and systemic hemodynamics. Although additional studies are needed to assess its clinical efficacy as a coronary dilator in the treatment of coronary artery disease, these data suggest a potential of ANP in the therapy of ischemia.     

Exaggerated atrial natriuretic peptide release during acute exercise in essential hypertension

The effects of acute exercise on plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and plasma renin activity (PRA) were studied in 13 patients with previously untreated essential hypertension, and 8 matched normotensive control subjects. Resting levels of ANP and PRA were similar in the two groups, while resting AVP concentrations were 1.4 times higher in hypertensive subjects. Graded exercise was performed on a bicycle ergometer with workload increased each minute until exhaustion (Wmax). Wmax was higher in normal subjects than in hypertensive patients. Blood pressure and heart rate rose more steeply in hypertensive patients. Plasma ANP increased during acute exercise in both groups, but the average increase in hypertensives was substantially greater than in normal subjects (P less than 0.05). The increase in ANP during exercise was greater in hypertensives with left ventricular (LV) hypertrophy, and there was a positive correlation between LV mass and the percentage rise in ANP during exercise (r = 0.56, P less than 0.005). Plasma AVP did not alter during exercise. Plasma renin concentrations showed a small rise during exercise in both groups, which was 16% less in hypertensive subjects (P less than 0.05). The enhancement of ANP release during exercise in hypertensive subjects may reflect both cardiac structural changes and increased redistribution of blood to the cardiopulmonary compartment.     

Pharmacokinetics of vasopressin and atrial natriuretic peptide in anesthetized rabbits

The elimination from plasma of the peptide hormones vasopressin (VP) and atrial natriuretic peptide (ANP) as well as the time course of release and elimination of these hormones after a physiological stimulus were studied in anesthetized rabbits. As an inverse relationship was found to exist between carotid sinus pressure and plasma IR-ANP, a decrease in carotid sinus pressure to 60 mm Hg was used to stimulate ANP as well as VP release. The elimination of VP after iv injection involved a rapid initial phase and a slow late component, with corresponding half-life (t1/2) values of 0.9 and 5.4 min, respectively. After reduction of carotid sinus pressure to 60 mm Hg, plasma VP increased significantly within 1 min and reached a maximum at 10 min. When carotid sinus pressure was increased to 160 mm Hg to inhibit VP release, the t1/2 of VP was 1.3 min. The t1/2 of immunoreactive (IR) ANP after iv infusion was 1.2 min. Plasma IR-ANP was significantly increased 2 min after carotid sinus pressure was decreased, and a maximum was observed at 10 min. The t1/2 of IR-ANP after elevation of carotid sinus pressure to 160 mm Hg was 3.2 min. These studies indicate that both VP and IR-ANP are rapidly eliminated in the anesthetized rabbit.     

Plasma atrial natriuretic factor in isolated systolic hypertension in the elderly: response to hypertonic saline infusion.

Plasma immunoreactive atrial natriuretic factor (ANF) and urinary sodium excretion were measured in elderly patients with isolated systolic hypertension (ISH) (n = 11), age-matched essential hypertensive patients (EHT; n = 16) and normotensive subjects (NT; n = 9) before and during a 60 min infusion of hypertonic saline (120 mEq of Na+). An exaggerated natriuresis during the sodium load was observed only in ISH. Baseline plasma ANF levels in ISH were significantly lower (P less than 0.05) than those of EHT and NT. There was no significant change in plasma ANF in EHT and NT subjects after the saline load. In contrast, there was a significant increase in plasma ANF (P less than 0.05) after the saline load in ISH. The change in urinary sodium excretion was significantly correlated with the change in plasma ANF (r = 0.75, P less than 0.01) in ISH. We conclude that an exaggerated natriuresis during a hypertonic saline infusion may be linked to an increase in plasma ANF in elderly ISH patients.     

Effects of plasma volume and osmolality on secretion of atrial natriuretic peptide and vasopressin in man

To clarify the role of blood volume and osmolality in the mediation of the release of atrial natriuretic peptide (ANP) and to examine the relationship between plasma ANP and plasma AVP levels in man, the effects of hypertonic saline and hypertonic mannitol infusion, and of water load on plasma levels of ANP and AVP were studied. Infusion of 5% saline to 7 healthy men at a rate of 0.05 ml.min-1.kg-1 for 2 h resulted in a parallel rise in plasma sodium, osmolality, plasma ANP and plasma AVP, indicating that plasma hyperosmolality stimulates secretion of both ANP and AVP. Infusion of 20% mannitol to 6 healthy men at the same rate resulted in a parallel increase in plasma osmolality, plasma ANP and AVP, whereas plasma sodium decreased, indicating that plasma hyperosmolality stimulates secretion of both ANP and AVP. Water load (20 ml/kg) into 7 healthy men produced a prompt and parallel fall in plasma sodium, plasma osmolality and plasma AVP. In contrast, plasma ANP and plasma volume, calculated from the changes in hematocrit, increased concomitantly, which indicates that expanded plasma volume stimulates secretion of plasma ANP. These results suggest that secretion of ANP in man is regulated principally by plasma volume, which may be modulated by a change in plasma osmolality. AVP secretion, on the other hand, is controlled mainly by osmotic change and secondarily by plasma volume.     

普萘洛尔及其对映体血药浓度对血浆心钠素水平的影响

本文研究８名健康志愿者口服单剂量普萘洛尔（４０ｍｇ）和１２名健康志愿者口服多剂量普萘洛尔（８０ｍｇ／ｄａｙ×３）后；静息状态和踏车兴奋状态时血浆心钠素（ＡＮＰ）水平的变化。口服单剂量普萘洛尔后３ｈ，静息状态时血浆ＡＮＰ水平升高１９．４±１１．１ｎｇ／Ｌ（Ｐ＜０．０５）；而运动状态时血浆ＡＮＰ升高更为明显，为６４．８±４０．９ｎｇ／Ｌ（Ｐ＜０．０５）。血浆ＡＮＰ的变化与普萘洛尔对映体Ｓ（－）－ＰＰＬ和Ｒ（＋）－ＰＰＬ浓度均具有良好的线性相关性，相关系数分别为０．８５６３和０．７１９２。口服多剂量普萘洛尔停药后１２ｈ，血浆ＡＮＰ仍可维持较高水平，较基础对照值升高３９．９±２８．３ｎｇ／Ｌ（Ｐ＜０．０５）。此结果提示，普萘洛尔参与了血浆ＡＮＰ水平的调控，这种作用尚难以用β肾上腺素能效应进行解释，可能与抑制ＡＮＰ的体内降解过程有关。     

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure

BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF). MATERIALS AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN 相似文献   

Splanchnic disposal of human atrial natriuretic peptide in humans

In healthy men (n = 6), the splanchnic fractional extraction of human atrial natriuretic peptide (hANP), as determined by the hepatic venous catheter technique, was 75% under basal conditions resulting in a splanchnic uptake of hANP of 8.5 +/- 5.0 pmol/min. In spite of a drop (P less than .05) in splanchnic fractional extraction to about 50%, splanchnic uptake of hANP rose to 56 to 99 pmol/min (P less than .01) when pharmacologic plasma concentrations of hANP were induced during a bolus (100 micrograms)-primed intravenous (IV) infusion (100 micrograms/h; time, one hour) of hANP. This was accompanied by a fall in estimated hepatic blood flow (P less than .05), in pulmonary arterial pressure (P less than .01), and, in each individual, in systemic BP. Total metabolic clearance rates, splanchnic clearance rates, and production rates of hANP were 4.5 +/- 2.2 L/min, 0.4 +/- 0.1 L/min, and 46.1 +/- 20.1 pmol/min, respectively. Thus, in healthy men, the splanchnic area accounts for approximately 10% of total hANP clearance.     

Coronary hemodynamic effects of atrial natriuretic peptide in humans

Studies of the effects of atrial natriuretic peptide on the coronary circulation have yielded conflicting results in animals and have not been fully investigated in human subjects. To further characterize the direct coronary hemodynamic actions of atrial natriuretic peptide in humans and to assess the safety of its administration in patients with coronary artery disease, incremental doses of synthetic atrial natriuretic peptide and nitroglycerin were infused into the left coronary artery in 14 patients, 11 of whom had coronary artery disease. Both agents caused dose-related increases in total coronary sinus blood flow. The largest dose of atrial natriuretic peptide given to all patients (100 micrograms) increased mean coronary sinus blood flow from 127 +/- 7 to 149 +/- 9 ml/min (p less than 0.05) and decreased coronary vascular resistance from 0.93 +/- 0.07 to 0.81 +/- 0.05 mm Hg/ml per min (p less than 0.05); mean arterial blood pressure and heart rate were not affected by this dose of atrial natriuretic peptide. The greatest changes in coronary sinus blood flow (+25%) and coronary vascular resistance (-18%) after atrial natriuretic peptide administration occurred in the patients with coronary artery disease and no other associated cardiovascular disease. The maximal effects of atrial natriuretic peptide were similar to those of nitroglycerin, and no untoward effects were observed. Thus, atrial natriuretic peptide is a direct coronary vasodilator in humans. Its maximal dose effects are similar to those of nitroglycerin and were well tolerated in this small group of patients. The physiologic importance and therapeutic potential of atrial natriuretic peptide in patients with coronary artery disease merit further investigation.     

Pressure-dependent,enhanced natriuretic response to low-dose,atrial natriuretic peptide infusion in essential hypertension

Abstract. Objective. To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent. Design. Part 1. The renal effects of a low-dose continuous infusion (10 ng kg^?1 min^?1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP + placebo (Part 1). Methods. Lithium clearance was used to estimate the proximal tubular reabsorption of sodium. Results. Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+ 102 vs. + 38%; P < 0.05), fractional excretion of sodium (+ 80 vs. + 37%; P < 0.05), and urinary output (+ 56 vs. + 8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (C_L1) increased and FE_L1 tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5′-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+ 51 vs. +99%; P <0.05). The relative changes in GFR, C_L1, and FE_L1 during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure. Conclusions. Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH is secondary in some degree to the elevated systemic pressure.     

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.