BASAL AND SALINE-STIMULATED LEVELS OF PLASMA ATRIAL NATRIURETIC FACTOR IN ACROMEGALY

We have studied plasma ANF before and after a 4-h intravenous infusion of normal saline in eight subjects with active acromegaly and in eight age and sex-matched control subjects. Plasma ANF, serum aldosterone and blood pressure were measured basally and after 2 and 4 h and plasma renin activity basally and after 4 h. Basal plasma ANF was similar in each group (4.4 +/- 1.5 pmol/l (mean +/- SEM) in acromegalic subjects and 5.3 +/- 0.7 pmol/l in controls NS). Plasma ANF did not rise significantly after saline in the acromegalic group (2-h value, 5.9 +/- 0.9; 4-h value, 5.1 +/- 0.9 pmol/l) but did rise significantly in the control group (2-h value, 8.9 +/- 1.9; 4-h value 9.5 +/- 1.3 pmol/l, both values P less than 0.05 vs basal level). The 4-h ANF value was significantly higher in the control group than in the acromegalic group (P less than 0.05). Basal and stimulated serum aldosterone values were similar in the two groups. Plasma renin activity suppressed to a lesser extent in the acromegalic group after 4 h. The facts that basal plasma ANF was not raised in acromegalic subjects and did not respond to saline stimulation demonstrate that an abnormality of ANF control may be an important factor in the aetiology of the expanded sodium status of patients with acromegaly and hence may contribute to the hypertension seen in patients with growth hormone excess.     

Plasma levels of atrial natriuretic factor in mild to moderate hypertensives without signs of left ventricular hypertrophy: correlation with the known duration of hypertension

The relationship between plasma atrial natriuretic factor (ANF), blood pressure (BP), age, plasma renin activity (PRA) and urinary sodium excretion was studied in 64 normal subjects (mean age 48.7 +/- 2.1 yrs; BP: 126.5 +/- 1.6/79.5 +/- 0.9 mmHg) and in 104 untreated uncomplicated essential hypertensives (50.8 +/- 1.1 yrs; BP: 164.7 +/- 1.6/105.2 +/- 0.6 mmHg). ANF was measured by radioimmunoassay after extraction on C18 columns. ANF was significantly higher in the hypertensives than in the normal subjects (37.1 +/- 1.2 vs 29.7 +/- 1.5 pg/ml, P less than 0.01). In normals plasma ANF was significantly correlated with age (r = 0.72, P less than 0.001), Na excretion (r = 0.42, P less than 0.001) and PRA (r = -0.71, P less than 0.001) whereas in the hypertensives ANF plasma levels correlated only with systolic (r = 0.46, P less than 0.001) and diastolic (r = 0.51, P less than 0.001) BP. In addition in hypertensive patients, by multivariate linear regression analysis, a significant correlation was found between age, known duration of hypertension and plasma ANF. The partial correlation coefficient between duration of hypertension and plasma ANF was highly significant (r = 0.80, P less than 0.001). These findings suggest that in essential hypertension the level of arterial BP is a main determinant of the ANF plasma values offsetting the ability of other physiological factors to regulate plasma ANF levels.     

RELEASE OF ATRIAL NATRIURETIC PEPTIDE DURING HYPERTONIC SALINE INFUSION: THE IMPORTANCE OF POSTURE

It is well known that atrial distension is an important stimulus for atrial natriuretic peptide (ANP) release, but conflicting evidence exists as to whether hyperosmolality also stimulates the release of atrial natriuretic peptide (ANP) in man. As infusion of hypertonic saline causes an increase in both blood volume and plasma osmolality, we have employed this stimulus to investigate: (i) whether hyperosmolality increases plasma ANP concentrations; (ii) the importance of posture in ANP release. Normal male volunteers (n = 6) were infused with hypertonic saline at a rate of 0.06 ml/kg/min for 2 h on two different occasions separated by 1 month. Infusion was performed with subjects in the seated and supine positions in random order. Hypertonic saline infusion induced increases in plasma osmolality (P less than 0.001), plasma sodium (P less than 0.01) and blood volume (P less than 0.001) in both seated and supine position. The increase in plasma osmolality was accompanied by an increase in plasma ANP during the supine infusion (2.7 +/- 1.0 to 9.0 +/- 2.4 pmol/l (mean +/- SEM; P less than 0.01] but no significant change in plasma ANP concentration occurred during the seated infusion. A positive linear correlation was obtained between increase in plasma osmolality and plasma ANP in the supine but not in the seated hypertonic saline infusion. There was a positive linear correlation between estimated increase in blood volume and plasma ANP in the supine but not the seated infusion of hypertonic saline. We suggest that the increase in ANP during hypertonic saline infusion reported by some workers was due to atrial distension, secondary to increased blood volume and is dependent on the position in which the subjects were studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction of angiotensin converting enzyme inhibition and atrial natriuretic factor

The interaction of angiotensin converting enzyme (ACE) inhibition and atrial natriuretic factor (ANF) was investigated in six supine, sodium-replete, normal volunteers who received captopril (10 mg i.v. bolus followed by 10 mg/hr constant infusion) or vehicle superimposed on background 3-hour, constant, low-dose (1.5 pmol/kg/min) infusions of human ANF (99-126). Plasma converting enzyme activity was significantly inhibited but this had no effect on endogenous plasma ANF concentrations. ANF infusions, with or without captopril, caused similar increases in plasma ANF concentrations, and calculated metabolic clearance rates for ANF were unchanged. Similarly, blood pressure, heart rate, renal blood flow, glomerular filtration rate, and renal electrolyte excretion, including ANF-induced natriuresis, were unaffected by captopril. The combination of ANF plus captopril produced a significant increase in plasma aldosterone (79 +/- 8 vs. 60 +/- 6 pmol/l, p less than 0.05), cortisol (406 +/- 52 vs. 265 +/- 29 nmol/l, p less than 0.01), adrenaline (119 +/- 21 vs. 76 +/- 10 pg/ml, p less than 0.05), and noradrenaline (319 +/- 49 vs. 215 +/- 38 pg/ml, p less than 0.05) compared with time-matched placebo data. Converting enzyme inhibition, in the absence of major changes in blood pressure or renal blood flow, has little effect on ANF metabolism or renal bioactivity. However, ACE inhibition and ANF combined may interact to increase activity of the hypothalamo-pituitary-adrenal axis and sympathetic nervous system by unknown mechanisms.     

Cardiovascular, renal and endocrine responses to low doses of atrial natriuretic factor in mild essential hypertension

The purpose of this study was to evaluate the cardiovascular, renal and endocrine effects of human atrial natriuretic factor (ANF), infused at a rate of 0.8 microgram/min (about 4 pmol/kg/min) for three hours in normal subjects and patients with essential hypertension. This infusion rate was chosen to obtain a range of plasma ANF levels which can be generated by physiological manoeuvres and to reduce the likelihood of hypotension. Five patients and six healthy volunteers participated in the study. The infusion had to be prematurely discontinued in one patient and in one control because of hypotension with relative bradycardia. Blood pressure otherwise remained unchanged during infusion whereas heart rate rose transiently. Plasma ANF levels increased similarly during infusion from 8.9 +/- 2.6 to 23.9 +/- 6.4 pmol/l in patients and from 3.7 +/- 0.7 to 25.4 +/- 6.9 pmol/l in the controls, remained stable during the infusion, and decreased similarly in both groups after the infusion, with a half-life of 7 min. Plasma guanosine cyclic phosphate (cGMP) was augmented by about four-fold in both groups. In both groups, plasma aldosterone levels fell whereas plasma noradrenaline increased. The diuretic effect of ANF was similar in both controls and patients (1354 +/- 161 vs 1542 +/- 116 ml/3 hrs respectively), whereas its natriuretic effect was exaggerated in hypertensive patients (90 +/- 11 vs 62 +/- 9 mmol/3 hrs, P less than 0.05). In conclusion, this low infusion rate of ANF produced similar changes in plasma ANF, cGMP, aldosterone and noradrenaline levels but patients with mild essential hypertension demonstrated an exaggerated diuretic and natriuretic response to ANF infusion.     

Plasma neuropeptide Y (NPY) and galanin before and during exercise in type 1 diabetic patients with autonomic dysfunction.

Plasma neuropeptide Y (NPY), plasma galanin and plasma catecholamines were determined before and during an ergometer exercise test in 11 type 1 diabetic patients (age 19-36 years, mean 30; duration of diabetes 2-18 years, mean 9) with autonomic dysfunction and in 13 age-matched healthy controls (age 24-36 years, mean 29). Before exercise, plasma NPY (100 +/- 6 pmol/l vs 144 +/- 7 pmol/l; P less than 0.001) and plasma galanin (54 +/- 3 pmol/l vs 77 +/- 5 pmol/l; P less than 0.005) were significantly lower in patients than in controls. During exercise, plasma NPY, plasma adrenaline, and plasma noradrenaline increased in patients and controls while galanin only increased in patients. Since there was a direct correlation between plasma NPY before exercise and the increment (delta 80%) in noradrenaline during exercise (r = 0.54; P less than 0.01), it is suggested that plasma NPY determined in the basal situation may be a useful marker of sympathetic nerve failure in diabetic patients.     

Plasma insulin levels do not change during atrial natriuretic factor infusion in human essential hypertensives

In order to evaluate the effects of atrial natriuretic factor (ANF) infusion on plasma insulin (IRI) in hypertension, 32 essential hypertensives (aged 40 to 62 years) were studied. After 1 week of pharmacologic washout under normal sodium intake (120 mEq of Na+/day), patients were randomly assigned to receive either ANF (0.04 micrograms/kg/min) or its vehicle (50 mL of isotonic saline) over a 60-min period in supine position. Plasma IRI and glucose were measured at -60, 0, 20, 40, 60, 120, 180, and 240 min (infusion time: from 0 to 60 min). Plasma levels of IRI and glucose did not change significantly during ANF infusion. On the contrary, after ANF discontinuation plasma IRI rose from levels of 13.5 +/- 6.4 microU/mL at 60 min to values of 20.1 +/- 11.3 microU/mL at 240 min (P less than .0001 v time 0). Plasma glucose showed a similar behavior, increasing from values of 100.4 +/- 5.0 mg/dL at 60 min to values of 120.0 +/- 5.1 mg/dL at 240 min (P less than .02 v time 0). Our findings suggest that ANF did not influence insulin release in hypertensives. The increase of plasma glucose and IRI observed after ANF discontinuation could be due to the relapse of sympathetic activity, suppressed during ANF infusion.     

A multicenter double-blind comparative study of rilmenidine and clonidine in 333 hypertensive patients

The efficacy and acceptability of rilmenidine were studied in a double-blind clonidine-controlled multicenter trial; after a 4-week placebo run-in period, patients with supine diastolic blood pressure (BP) between 95 and 115 mm Hg received as monotherapy either rilmenidine or clonidine over 6 weeks. The initial dose (rilmenidine 1 mg/day or clonidine 0.15 mg/day) was doubled (1 mg or 0.15 mg twice a day, respectively) after 2 weeks if diastolic BP remained greater than or equal to 90 mm Hg. Three hundred and thirty-three patients (mean age 57.8 +/- 0.7 years) with a systolic BP of 170.53 +/- 0.92 mm Hg and a diastolic BP of 101.57 +/- 0.30 mm Hg were randomly divided into 2 homogenous groups (rilmenidine, n = 162 and clonidine, n = 171). All patients taking rilmenidine completed the trial. Seventeen patients taking clonidine (10%, p less than 0.01 vs rilmenidine) were withdrawn because of severe side effects. Systolic and diastolic BP were significantly reduced in both groups at every examination (at 2, 4 and 6 weeks). The mean decreases in supine and erect BP were identical in both groups: systolic BP 19 mm Hg and diastolic BP 12 mm Hg after 6 weeks. BP was normalized (systolic BP less than 160 and diastolic BP less than or equal to 90 mm Hg) in 57% of patients taking rilmenidine and 56% of patients taking clonidine (60% of normalized patients had been taking the single dose in both groups).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of posture on clearance of atrial natriuretic peptide from plasma

The effect of posture on plasma atrial natriuretic peptide (ANP) levels during a constant iv infusion of the 28-amino acid polypeptide was investigated in 8 normal men. alpha-Human ANP was infused at a constant rate of 0.5 micrograms/min (162 pmol/min) while the men were supine, then erect, and finally when supine again. Plasma ANP levels rose from 10.9 +/- 1.6 (+/- SEM) to 33.3 +/- 2.4 pmol/L after 60 min of constant infusion with the men in the supine position. On standing, plasma ANP increased further to 40.6 +/- 3.4 pmol/L, then fell to 32.2 +/- 2.7 pmol/L with resumption of supine posture. The calculated MCR of ANP fell from a mean of 7.7 to 5.7 L/min on standing, but rose again to 7.6 L/min upon lying down. We conclude that body posture has a significant effect on the rate of clearance of ANP from plasma.     

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.     

Comparison of the effects of ANF 99–126 and ANF 103–126 on captopril-induced renin release in man

OBJECTIVE: The aim was to examine the effects of atrial natriuretic factor (ANF) 99-126 and ANF 103-126, an N-terminal shortened analogue of the peptide, on the plasma renin activity response to captopril, an inhibitor of angiotensin-converting enzyme. DESIGN: Two protocols were performed. In the first protocol, subjects were studied on three occasions. Captopril 25 mg was given and a 60 minute infusion of 5% D-glucose (placebo), or ANF 99-126 3 or 10 pmol/kg/min, was administered in a single blind randomized manner. The second protocol was divided in two parallel phases comparing ANF 103-126 either 3 or 10 pmol/kg/min to placebo. SUBJECTS: Thirty-three salt-replete healthy male volunteers aged 21-39 years were studied in the supine position. MEASUREMENTS: Plasma renin activity, plasma ANF 99-126 and ANF 103-126 levels, heart rate and blood pressure were measured. RESULTS: Compared to placebo infusion, the rise in plasma renin activity after captopril was attenuated by ANF 99-126 infusion (from 755% of baseline to 294% by ANF 99-126 3 pmol/kg/min and from 755 to 202% by 10 pmol/kg/min; P less than 0.03 and P less than 0.01 respectively). The comparable findings with ANF 103-126 were 492 to 218% (3 pmol/kg/min) and 645 to 364% (10 pmol/kg/min) (P less than 0.01 and P less than 0.01 respectively). CONCLUSIONS: The results, taken in conjunction with previous findings, suggest that atrial natriuretic factor inhibits in a non-selective manner the renin response to all secretagogues so far tested in man. The current results also suggest that the anti-renin action of atrial natriuretic factor does not depend on the first four N-terminal amino acids of the native peptide.     

Low-dose infusion of atrial natriuretic factor in mild essential hypertension

Intra-arterial blood pressure, cardiac output, heart rate, right heart indexes, urinary electrolytes, and urinary volume were monitored in eight patients with untreated (WHO Class I) essential hypertension. The patients were given synthetic atrial natriuretic factor (ANF) (99-126 alpha-hANP) at 1 and 2 pmol/kg/min in series (phases 1 and 2, 2 hours each dose) or vehicle (hemaccel) in random order on two separate occasions while on their usual diet. Arterial plasma ANF levels increased significantly from basal and time-matched placebo values from 25 +/- 2 and 28 +/- 3 pmol/l to 50 +/- 4 and 83 +/- 9 pmol/l at the end of phases 1 and 2, respectively (p less than 0.001). After 30 minutes during phase 2, systolic blood pressure decreased significantly by 20 +/- 4 mm Hg (p less than 0.001) from basal and time-matched placebo values and remained significantly reduced (-17 +/- 4 mm Hg, p less than 0.001) by the end of the recovery period (2 hours after infusions were completed). Pulmonary systolic blood pressure decreased by 5 +/- 1 mm Hg (phase 2, p less than 0.05). Cardiac output decreased by 0.5 +/- 0.1 l/min below baseline at the end of phase 2 of ANF infusion, whereas it increased significantly (p less than 0.02) by 0.6 +/- 0.1 l/min during vehicle infusion. Systemic diastolic, pulmonary diastolic, right atrial, and wedge pressures were not significantly changed during ANF or vehicle infusions, nor were pulmonary vascular resistance or heart rate altered. Systemic vascular resistance did not change significantly during both infusions, whereas during recovery, systemic vascular resistance decreased significantly after ANF infusion was discontinued (p less than 0.05). Microhematocrit levels increased dose dependently during ANF. The maximum increase was observed at the end of phase 2 (+4.7 +/- 1.7%), whereas the microhematocrit level decreased to -2.4 +/- 0.6% with vehicle (p less than 0.001) at the end of phase 2. Urinary sodium excretion increased significantly (p less than 0.02) by the end of phase 2 under ANF infusion (+38 +/- 15%), whereas it decreased (-10 +/- 6%) under placebo infusion by the end of phase 2. Urinary magnesium excretion was significantly increased during ANF infusion from phase 1 (p less than 0.02), whereas urinary potassium levels, calcium levels, creatinine levels, volume, and glomerular filtration rate did not differ significantly between the two infusions. Plasma renin, angiotensin II, aldosterone, and catecholamine concentrations did not change significantly during ANF or vehicle infusions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasma atrial natriuretic factor levels during normal pregnancy and pregnancy complicated by diabetes mellitus and hypertension

Atrial natriuretic factor (ANF) may play a role in the regulation of the changes of blood volume and vascular reactivity during pregnancy and when pregnancy is complicated by hypertension. Reports of plasma ANF levels during pregnancy are conflicting. We have prospectively studied plasma ANF levels during pregnancy in 25 women, and compared these with 20 age-matched non-pregnant women. Five women developed hypertension during pregnancy and a further five who remained normotensive had insulin-dependent diabetes mellitus. Plasma ANF was 6.8 +/- 1.2 (mean +/- SEM) and 6.3 +/- 0.9 pmol/l during weeks 8-15 and 24-31 of normal pregnancy (n = 15; vs non-pregnant levels (4.0 +/- 0.6 pmol/l) P less than 0.05, n = 20). Levels were 4.3 +/- 0.8 and 3.9 +/- 0.4 pmol/l during weeks 16-23 and 32-39. In the diabetic patients and in the group who developed hypertension levels were at no time different from the uncomplicated pregnancy group. Serum aldosterone increased as pregnancy progressed, but plasma renin activity remained unchanged. As plasma ANF was not different between those who did, and those who did not develop hypertension, early measurement of it will not predict who will and who will not develop hypertension during pregnancy.     

Effect of reducing atrial pressure on atrial natriuretic factor and vasoactive hormones in congestive heart failure secondary to ischemic and nonischemic dilated cardiomyopathy

The effect of an acute and sustained reduction in atrial pressure on atrial natriuretic factor (ANF) and vasoactive hormone secretion was studied in 9 patients with congestive heart failure (CHF). Intravenous nitroglycerin was titrated to reduce the pulmonary artery wedge pressure by 30 to 50% and maintain this reduction for 4 hours. After 60 minutes of nitroglycerin administration, the mean decrement in wedge pressure was 10.0 +/- 1.7 (standard error) mm Hg (35%) and plasma ANF was 65.3 +/- 13.9 pmol/liter (35%). The initial decrease, sustained reduction and later increase in plasma ANF levels closely paralleled the changes in pulmonary arterial wedge (r = 0.94, p less than 0.0001) and right atrial pressures (r = 0.91, p less than 0.0001) during and immediately after the nitroglycerin infusion. Plasma aldosterone and cortisol levels increased during the first 2 hours of the nitroglycerin infusion, but there was little change in plasma norepinephrine or plasma renin activity. Although levels were elevated in CHF, plasma ANF still responded rapidly to changes in atrial pressure. A sustained reduction in pressure produced a sustained reduction in ANF levels. These findings provide further support for a regulatory role of ANF, even in chronic CHF.     

THE EFFECT OF OXYTOCIN INFUSION ON ADENOHYPOPHYSIAL AND ADRENAL CORTICAL RESPONSES TO INSULIN-INDUCED HYPOGLYCAEMIA

The responses of plasma adrenocorticotrophin (ACTH), cortisol, growth hormone (GH) and prolactin to insulin-induced hypoglycaemia were studied in six lean male subjects (age 22-29 years). Intravenous insulin tests were performed with and without oxytocin infusion. Blood sugar nadir occurred at the onset of symptoms (time S) with no significant differences between oxytocin and saline infusion. During the oxytocin infusion mean plasma oxytocin increased from 1.9 pmol/l to 138 pmol/l. Peak increase in plasma ACTH (oxytocin 266 +/- 54 ng/l; saline 281 +/- 43 ng/l, mean +/- SEM) was at S + 10 min while peak plasma cortisol (oxytocin 680 +/- 47 nmol/l: saline 656 +/- 40 nmol/l) was measured at S +/- 60 min, peak GH (oxytocin 96 +/- 17.8 mU/l; saline 106 +/- 18.6 mU/l) at S + 60 min and prolactin (oxytocin 1332 +/- 239 mU/l; saline 1242 +/- 273 mU/l) at S + 30 min. There were no significant differences in plasma concentrations of ACTH, cortisol, GH or prolactin between saline and oxytocin infusion. The results indicate that oxytocin has no effect on plasma ACTH, cortisol, GH and prolactin responses to insulin-induced hypoglycaemia. In particular they fail to support previous studies which suggested an inhibitory role for oxytocin in ACTH secretion.     

Osmoregulation of arginine-8-vasopressin secretion in primary hypothyroidism and in Addison's disease

The osmoregulation of arginine-8-vasopressin (AVP) was investigated in 14 patients with primary hypothyroidism and in 6 with Addison's disease. Plasma AVP was measured by radioimmunoassay. Patients with primary hypothyroidism were classified into subgroups with elevated (6.81 +/- 1.12 pmol/l) or normal (3.92 +/- 0.96 pmol/l) basal levels of plasma AVP. Following the infusion of 2.5% saline, a positive correlation was established between plasma AVP and plasma osmolality. A decreased osmotic threshold was found in hypothyroid patients with augmented basal AVP levels (pAVP = 0.37 (pOs-265), r = 0.71, P less than 0.01) as compared with that in hypothyroid patients with a normal AVP level (pAVP = 0.42 (pOs-280), r = 0.93, P less than 0.001). A relationship was demonstrated between the alteration in the AVP osmoregulation and the severity of the thyroid insufficiency. Patients with Addison's disease exhibited an increased basal level of plasma AVP (9.59 +/- 1.25 pmol/l) and a decreased osmotic threshold (pAVP = 0.42 (pOs-261), r = 0.63, P less than 0.01) contrasted to that of healthy volunteers (pAVP = 0.41 (pOs-280), r = 0.83, P less than 0.001). The osmoregulation disturbance of the AVP secretion may play a major role in the impaired water metabolism in primary hypothyroidism and in Addison's disease.     

Atrial natriuretic factor, cardiac volumes and filling pressures during exercise in congestive heart failure.

To study the mechanism of atrial natriuretic factor (ANF) release in heart failure, we measured plasma ANF concentrations, cardiac volumes and filling pressures at rest and during three graded exercise levels (E1, E2, E3) in six male patients with congestive heart failure (CHF) and compared them with 13 normal male subjects. At rest, ANF concentrations were sixfold higher in patients with CHF than in normal subjects (at rest: 53 +/- 12 vs 8 +/- 1 pmol.l-1; P less than 0.02). End-systolic ventricular volumes were increased threefold in patients with CHF (P less than 0.02) despite normal mean central venous pressure, pulmonary artery pressure (PAP) and pulmonary wedge pressure (PWP). A positive correlation was found between end-systolic ventricular volumes and plasma ANF (r = 0.93, P less than 0.001). During exercise, ANF rose by 120% over basal values both in patients with CHF and in normal subjects (P less than 0.01). Volumes higher than normal in patients with CHF increased further at E2 (P less than 0.05) in contrast to a decrease of systolic volumes recorded in normal subjects (P less than 0.05). Filling pressures rising abnormally in patients with CHF correlated with plasma ANF during exercise (r = 0.53, P less than 0.02 for PAP; r = 0.51, P less than 0.05 for PWP). In conclusion, our data suggest that ANF release in CHF is regulated at rest by cardiac volumes when filling pressures are still normal. During exercise, ANF release is not impaired in CHF with normal rest filling pressures and is regulated during exercise by left filling pressures.     

Antihypertensive effect of sustained-release isosorbide dinitrate for isolated systolic systemic hypertension in the elderly

A double-blind, randomized trial was performed in 40 patients, mean age (+/- standard deviation) 80 +/- 4 years, with isolated systolic systemic hypertension to evaluate the antihypertensive effect of oral sustained-release isosorbide dinitrate (ISDN), 20 to 40 mg twice daily, vs placebo. After 12 weeks of treatment, supine systolic blood pressure (BP) decreased from 192 +/- 10 to 162 +/- 12 mm Hg with ISDN (p less than 0.001) and from 189 +/- 10 to 175 +/- 15 mm Hg with placebo (p less than 0.001). On the basis of variance analysis, the decrease in systolic BP was significantly lower with ISDN (27 mm Hg) than with placebo (13 mm Hg). Similar results were observed for supine and erect systolic BP measured at 8 AM and 4 PM, 8 and 12 hours after drug intake. No significant differences in diastolic BP, heart rate or side effects occurred. After the ISDN tapering off-period (2 weeks), systolic BP increased significantly but did not change with placebo. The study provided evidence that in elderly patients with systolic hypertension, sustained-release ISDN induced a selective and sustained decrease in systolic BP, antihypertensive effect was observed 8 and 12 hours after drug administration, and no tolerance phenomenon was noted.     

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.     

Basal and saline-stimulated plasma atrial natriuretic hormone in Cushing's syndrome

The pathogenesis of hypertension associated with Cushing's syndrome is incompletely understood. We have studied basal and saline-stimulated levels of plasma atrial natriuretic hormone in 10 subjects with active Cushing's syndrome (8 F: 2 M), aged 43 +/- 4 years (mean +/- SEM). Ten age- and sex-matched normal control subjects were also studied. Subjects fasted from 22.00 h, rose at 07.45 h, and remained ambulant until 09.45 h when blood was taken for plasma ANH, plasma renin activity and serum aldosterone. Subjects then rested supine until 10.00 h when blood was again taken, and blood pressure recorded. Then, while subjects remained supine, 21 of 0.9% NaCl were infused between 10.00 and 14.00 h. Blood was taken hourly. Basal plasma ANH was 8.0 +/- 0.9 pmol/l in Cushing's subjects and 6.9 +/- 2.5 pmol/l in controls. Levels increased in response to saline in both groups, and became significantly higher in the group of patients with Cushing's syndrome (14.00 h level 21.3 +/- 3.9 vs 10.4 +/- 1.9 pmol/l; p less than 0.05). Serum aldosterone and plasma renin activity were not different between groups. Mean blood pressure was higher in patients (114 +/- 4 vs 91 +/- 7 mmHg; p less than 0.05). Urinary sodium excretion was not different between groups before saline, but during the four hours of saline was higher in Cushing's subjects (133 +/- 12 vs 67 +/- 11 mmols; N = 6; p less than 0.05). Our results suggest that during salt loading the exaggerated natriuresis seen in the Cushing's group may have been caused by ANH.