Higher Plasma Atrial Natriuretic Factor Research Articles

Atrial natriuretic factor binding to its receptor is dependent on chloride concentration: A possible feedback-control mechanism in renal salt regulation.

Although considerable evidence indicates a role for atrial natriuretic factor (ANF) in renal salt regulation, other studies have found a lack of natriuretic response to high-plasma ANF under certain physiological and pathophysiological conditions. The mechanism for this apparent insensitivity to ANF is unknown. In the present study, it was found that ANF binding to its receptor requires the presence of chloride and occurs in a chloride concentration-dependent manner. ANF binding was measured using the purified recombinant hormone-binding domain of the ANF receptor in the presence of 0.1 mol/L NaCl or other selected salt. High specific binding was detected in the presence of NaCl, KCl, or NH(4)Cl. However, binding was undetectable when the salt was replaced with NaHCO(3), CH(3)COONa, or CH(3)COONH(4), indicating that binding requires the presence of chloride. Chloride dependence was also found with the native receptor in bovine adrenocortical membrane preparations. ANF binding to the recombinant protein was chloride concentration-dependent over a range from 0.05 to 10 mmol/L, and a half-maximum binding was attained at approximately 0.6 mmol/L equivalent chloride concentration. Competitive-binding assays at several fixed concentrations of NaCl showed that lowering chloride concentration caused a decrease in maximum binding but did not alter K(d) values, suggesting that a loss of chloride turns off ANF binding rather than reducing affinity for ANF. Saturation-binding studies showed that excess ANF cannot overcome loss of binding caused by low chloride. Chloride-dependent ANF-receptor binding may function as a feedback-control mechanism regulating the ANF-receptor action and, hence, renal sodium excretion.

Effects of a three-day head-down tilt on renal and hormonal responses to acute volume expansion.

To clarify whether exposure to 6 degrees head-down tilt (HDT) leads to alterations in body fluid volumes and responses to a saline load similar to those observed during space flight we investigated eight healthy subjects during a 4-day, 6 degrees HDT and during a time-control ambulatory period with cross-over. Compared with the ambulatory period, HDT was associated with greater urinary excretion of water and sodium (UV, U(Na)V) from 0 to 12 h (cumulated UV 1,781 +/- 154 vs. 1,383 +/- 170 ml, P < 0.05; cumulated U(Na)V 156 +/- 14 vs. 117 +/- 9 mmol, P < 0.05), and with higher plasma atrial natriuretic factor (ANF) at 4 h. Hemoglobin and hematocrit increased over the first 24 h, and blood and plasma volumes were decreased after 48 h of HDT (P < 0.05). Plasma renin activity (PRA) and aldosterone did not differ between the two groups. With prolongation of HDT, UV and U(Na)V returned close to baseline values. On the fourth HDT day, a 30-min infusion of 20 ml/kg isotonic saline was performed, while a large oral water load maintained a high urine output. The ambulatory period experiment was done with the subjects in the acute supine posture. Sodium excreted within 4 h of loading was 123 +/- 8 mmol during HDT vs. 168 +/- 16 mmol during the ambulatory period (P < 0.05). The increase in plasma ANF and decrease in PRA were greater during HDT than during the ambulatory period (ANF 30 +/- 5 vs. 13 +/- 4 pg/ml, P < 0.05; PRA -1.4 +/- 0.4 vs. -0.5 +/- 0.2 ng. ml(-1). h(-1), P < 0.05). Our data suggest that after a 3-day HDT period, thoracic volume receptor loading returns to the level seen in the upright position, leading to blunted responses to volume expansion, compared with acute supine control.

Acute enoximone effect on systemic and renal hemodynamics in patients with heart failure.

Patients with heart failure generally show improvement in their clinical condition after enoximone infusion over the period of treatment; this effect cannot be ascribed only to the known hemodynamic action of this drug. Thirty-six patients (age range 44-82 years) with heart failure (NYHA class II-IV) underwent 48-hour enoximone infusion to study whether this prolonged improvement might depend on changes in systemic or renal hemodynamics or in neurohormonal balance. All patients underwent Swan-Ganz hemodynamic monitoring; renal plasma flow, glomerular filtration rate, plasma atrial natriuretic factor (ANF), and plasma renin activity (PRA) were all measured at baseline, at the peak of the enoximone action, and 48 hours after drug discontinuation. The main hemodynamic parameters were significantly improved during enoximone infusion and after drug discontinuation. The cardiac index basal value of 2.2 +/- 0.1 l/min/m2 increased to 3.1 +/- 0.1 l/min/m2 after 24-hour therapy (p < 0.01); similarly, pulmonary wedge pressure, mean pulmonary arterial pressure, and right atrial pressure decreased markedly (p < 0.01). Beneficial effects were also observed in renal hemodynamics; indeed, renal plasma flow (basal value 485 +/- 39 ml/min) increased significantly after 24-hour enoximone infusion (575 +/- 35 ml/min; p < 0.01), and this tendency was also observed 48 hours after drug discontinuation. No significant modifications were observed in plasma hormone data; however, the PRA plasma level had a tendency to decrease. We conclude that in patients with heart failure, enoximone infusion has a less marked effect on renal hemodynamics, but this is more lasting than systemic hemodynamic effects. The tendency of PRA to decrease (although not statistically significant), still detectable 2 days after treatment in the presence of steady high plasma ANF concentrations, may also contribute to the paradoxical longlasting benefit despite the short-lived improvement in systemic hemodynamics after brief cycles of enoximone infusion.

Downregulation of atrial natriuretic factor clearance receptors in experimental chronic renal failure rats

Studies were performed to examine the changes of renal ANF second messenger guanosine 3',5'-cyclic monophosphate (cGMP) responses and receptor properties in chronic renal failure (CRF). Five-sixths-nephrectomized and sham-operated Wistar rats were used. The glomerular filtration rate was decreased in the five-sixths-nephrectomized rats, which also had significantly higher plasma blood urea nitrogen and plasma atrial natriuretic factor (ANF) levels (148.5 +/- 10.2 vs. 115.7 +/- 7.3 pg/ml, P = 0.01) than the sham rats. In vitro ANF-stimulated cGMP accumulations in glomeruli of five-sixths-nephrectomized rats were higher than controls. Radioligand-binding experiments showed downregulation of the total ANF receptor in both acid and nonacid wash CRF glomeruli (nonacid wash: 189 +/- 25 vs. 362.8 +/- 52.8 fmol/mg protein, P < 0.05; acid wash: 449.8 +/- 67 vs. 652.7 +/- 52.5 fmol/mg protein, P < 0.05). No change in receptor densities was observed in the des(Gln18,Ser19,Gly20,Leu21)atrial natriuretic peptide-(4--23)-NH2-resistant receptors between sham and CRF rat glomeruli. Therefore, downregulation of ANF clearance receptors exists in CRF rat glomeruli, and this is associated with the exaggerated ANF-stimulated cGMP response in these CRF glomeruli. Hypersensitivity of CRF rat to ANF, together with high plasma ANF levels and downregulation of clearance receptor, may contribute to increased sodium excretion in CRF.

Abnormalities in the renal and vascular responses to LBNP in humans with early diabetes.

Plasma atrial natriuretic factor (ANF) concentrations are increased in subjects with insulin-dependent diabetes mellitus (IDDM). A potential contribution of ANF to the maintenance of abnormalities in renal hemodynamic function has been considered but not proven in human diabetic subjects. The aim of these experiments was to determine the response of renal blood flow (RBF), glomerular filtration rate (GFR), filtration fraction (FF), and urinary sodium excretion (UNaV) to a reduction of plasma ANF concentrations induced by application of nonhypotensive lower body negative pressure (LBNP) in a group of subjects with early, uncomplicated, well-controlled IDDM compared with control subjects. Baseline supine measurements before LBNP revealed the diabetic subjects to have a significantly higher plasma ANF (31 +/- 2 vs. 24 +/- 2 pg/ml, P = 0.05). GFR tended to be higher (118 +/- 11 vs. 104 +/- 9 ml/min) and UNaV tended to be depressed (188 +/- 25 vs. 240 +/- 25 mumol/min) despite equal sodium intake, but not significantly so. In addition IDDM subjects exhibited significantly lower baseline plasma norepinephrine (PNE) concentrations (0.91 +/- 0.20 vs. 1.60 +/- 0.2 nmol/l, P = 0.03). Forearm vascular resistance (FVR) was not significantly different between the two groups (29 +/- 5 vs. 33 +/- 5 units). LBNP induced comparable decreases in ANF and central venous pressure (CVP) in both groups. The anticipated renal response to ANF reduction (declines in GFR, FF, and UNaV) occurred only in the normal control group. The percent decline in GFR (11% vs. 34.5%, P = 0.01) was markedly attenuated in IDDM subjects. The expected reflexive increase in PNE and FVR also did not occur in IDDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Atrial Natriuretic Factor in Obesity: Correlation to Echocardiography.

The plasma levels of atrial natriuretic factor (ANF), renin activity and aldosterone level in a lean control group (group I, n=20), obese normotensive individuals (group II, n=46), and obese hypertensives (group III, n=14) were estimated along with echocardiographic examination. According to findings obtained from echocardiography, normotensive and hypertensive obese subjects with impaired left ventricular diastolic function were subclassified as groups IIa and IIIa, respectively. ANF was found to be increased in obese normotensive and obese hypertensive groups compared with the control group level. Obese normotensive and obese hypertensive subjects with impaired left ventricular function were found to have higher plasma ANF than their unimpaired counterparts. An inverse relation was found between plasma ANF and plasma renin activity or aldosterone level. There were a significant decrease in fractional shortening and increase in left atrial diameter in groups IIa and IIIa compared with control group. We conclude that impairment of the left ventricular diastolic function caused by hypertrophy of the left ventricle in obese normotensives and obese hypertensives produces elevation of pressure in the left atrium and an increase in the secretion of ANF. Cardiac chamber in pressure is a reflection of this increased circulating ANF.

Plasma atrial natriuretic factor and blood pressure drops during hemodialysis.

The potential role of atrial natriuretic factor (ANF) in blood pressure (BP) drops during hemodialysis (HD) has been examined in 30 patients with end-stage chronic renal failure. Echocardiographic measurements and evaluation of cardiac parasympathetic function were performed prior to HD sessions, simultaneously with hormonal determinations. The plasma ANF level was correlated with the peak value of the E wave and the Doppler index of the left ventricular preload and was more elevated in 'denervated' than in intact patients. During the HD sessions, the BP fell in 18 patients (group 1) and remained stable in 12 others (group 2), despite similar weight losses. Both groups differed by the basal values of plasma ANF, greater in group 1 than in group 2 (100.0 +/- 13.3 vs. 65.7 +/- 3.4 fmol/ml; p < 0.05). The magnitude of plasma ANF decrease was identical in both groups despite the BP decrease in group 1 at the end of the session. These results suggest that the ANF release depends not only on hemodynamics but also on cardiac innervation in dialyzed patients and that high plasma ANF levels are implied in the BP drops during HD session.

Second Messenger Changes of Atrial Natriuretic Factor and Brain Natriuretic Peptide in Kidneys of Cardiomyopathic Hamsters

The effects of natriuretic peptides in kidney are blunted in congestive heart failure (CHF). The aim of this study is to examine the changes of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) second messenger productions in CHF. Experiments were conducted on 300-day-old normal and cardiomyopathic hamsters. Blood was collected for ANF measurement. cGMP accumulation studies were done in glomeruli upon ANF and BNP stimulation, and in inner medullary collecting duct (IMCD) cells upon ANF stimulation. Higher plasma ANF levels were found in cardiomyopathic hamsters (811.3 +/- 124.6 vs. 166.6 +/- 13 pg/ml, p < 0.01). ANF-stimulated cGMP accumulations in glomeruli and IMCD cells were higher in cardiomyopathic hamsters. Increased BNP-stimulated cGMP accumulations were also observed in cardiomyopathic hamster glomeruli. These results suggest that the renal hyporesponsiveness to natriuretic peptides in CHF in not due to attenuated ANF and BNP second messenger productions.

Characterisation of plasma and tissue atrial natriuretic factor during development of moderate high output heart failure in the rat.

The aims were (1) to characterise plasma and tissue atrial natriuretic factor (ANF) levels, haemodynamic variables, and renal function at different stages of moderate chronic high output heart failure in the rat; and (2) to assess the contribution of the atria and ventricles to plasma ANF levels. Plasma and tissue ANF levels, haemodynamics, and renal function were evaluated at 1, 2, 4, 8, and 16 weeks after the development of aorto-caval shunts. Sham operated animals served as controls at identical time points. Male Sprague-Dawley rats weighing 225-275 g were used in all experiments. Mean arterial blood pressure was lower and right atrial pressure was higher in the aorto-caval shunt groups than in sham operated controls at all time periods. Left ventricular end diastolic pressure was increased significantly in aorto-caval shunt rats at 1, 2, and 4 weeks when compared with their control counterparts. Plasma COOH terminal and NH2 terminal ANF concentrations were increased significantly in aorto-caval shunt animals. Plasma ANF was positively correlated with right atrial pressure and left ventricular end diastolic pressure in aorto-caval shunt rats but not in sham operated controls. Aorto-caval shunt animals also developed marked cardiac hypertrophy with decreased atrial ANF concentration, but not content, and increased ventricular ANF concentration and content. Despite high plasma ANF concentrations, aorto-caval shunt rats had a lower packed cell volume at all observed periods and reduced urinary sodium excretion and urinary volume at 1 and 2 weeks, with trends to a reduction at 4, 8, and 16 weeks. Body weight was higher in aorto-caval shunt animals at 16 weeks than in sham operated controls. (1) Chronically increased cardiac filling pressure stimulated not only ANF release but also ANF synthesis in each cardiac chamber, which in turn contributed to raised plasma ANF concentrations in aorto-caval shunt rats; (2) an attenuated renal response to endogenous ANF and sodium and water retention were apparent in A-C shunt rats. Activation of neurohormonal vasoconstrictor systems and gradually decreased plasma ANF concentrations may contribute to sodium and water retention at different stages of this experimental model of heart failure.

Alterations in the secretion of atrial natriuretic factor in atria from aged rats.

We measured plasma atrial natriuretic factor levels and atrial natriuretic factor secretion by isolated left atria from aging rats to determine the secretory response to stretch and adrenergic stimulation. Systolic arterial pressure and right atrial pressure were measured in vivo. Twenty-four hours later, atria were removed and studied in vitro in a perifusion system. After removal, stabilization at 0.7 g tension, and equilibration for 65 minutes, atria were stretched by increasing external tension for 20 minutes. After reequilibration atria were perifused with phenylephrine, 10(-5) M, for an additional 30 minutes. Right atrial pressure was not different between young (3 months) and aged (16-24 months) rats. Aged rats had higher plasma atrial natriuretic factor levels (52 +/- 8 versus 21 +/- 6 pmol/l; p less than 0.05) than young rats. Basal atrial natriuretic factor secretory rate in vitro was greater in atria from aged rats than young rats (875 +/- 35 versus 402 +/- 22 pg/min; p less than 0.05). Atria from aged rats had an increased response to phenylephrine compared with young rats (1,687 +/- 143 versus 788 +/- 113 pg/min; p less than 0.05) when means were adjusted for basal secretory rate. The secretory response to stretch was less than that of young rats (673 +/- 37 versus 773 +/- 27 pg/min), although this difference was not significant (p = 0.07). Atrial natriuretic factor secretion in response to adrenergic stimulation is increased with aging, and these secretory responses may contribute to increased plasma levels that occur during aging. In contrast to increased adrenergic responses, atrial natriuretic factor secretion after external stretch is not increased in aging rats.

Effects of atrial natriuretic factor on blood flow distribution and vascular resistance in conscious dogs

Systemic and regional hemodynamic responses to atrial natriuretic factor (ANF) administered by either bolus or infusion were examined in conscious dogs in the presence and absence of ganglionic blockade. In intact dogs, bolus injection of ANF (9 micrograms/kg), which increased plasma ANF by 100,913 +/- 12,330 pg/ml, initially reduced mean arterial pressure (7 +/- 1%) and total peripheral (-31 +/- 2%), coronary (-28 +/- 3%), mesenteric (-19 +/- 2%), renal (-36 +/- 2%), and iliac (-24 +/- 2%) vascular resistances. During the recovery period, resistance rose in the total peripheral (+13 +/- 3%), coronary (+19 +/- 5%), mesenteric (+7 +/- 2%), and iliac (+42 +/- 8%) beds but did not rise in the renal bed. At 15 min after infusion of ANF (0.3 micrograms.kg-1.min-1 x 30 min), which increased plasma ANF by 4,296 +/- 869 pg/ml, resistance rose in the total peripheral (+19 +/- 3%), coronary (+17 +/- 2%), mesenteric (+23 +/- 7%), and iliac (+40 +/- 11%) beds but remained slightly depressed in the renal bed (-8 +/- 5%). Ganglionic blockade with hexamethonium did not modify substantially the pattern of change of regional vascular resistances to ANF. Thus in conscious dogs, ANF under steady-state conditions was found to elicit direct vasoconstriction in most regional vascular beds and minor vasodilation in the renal vascular bed. However, after bolus administration of ANF, which results in extremely high plasma ANF levels, transient vasodilation occurs in all regional vascular beds. These data suggest that the distribution of ANF receptors, which elicit vasodilation, differs in regional vascular beds, and that in most vascular beds, except those of the kidney, these receptors require extremely high levels of ANF to be activated.

Plasma atrial natriuretic factor in patients with acute myocardial infarction

Plasma atrial natriuretic factor (ANF), renin activity (PRA), aldosterone and antidiuretic hormone (ADH) were determined in 16 patients with uncomplicated acute myocardial infarction (AMI) for 7 days in all patients and in six patients for 8 more days. Echocardiograms were performed and central venous pressure (CVP) was measured on the 2nd, 7th and 15th days. On admission, plasma ANF was higher in patients with AMI (129.8 +/- 70.6 pg ml-1, mean +/- SD) than in healthy volunteers (50.6 +/- 10.0 pg ml-1) (P less than 0.05). Arterial pressure, heart rate, CVP were normal. Left atrial (LAD) and left ventricular diameters (LVDD) were increased in six patients. Ejection fraction (EF) was reduced in all. A significant inverse relationship between ANF and EF was observed. Patients with EF less than or equal to 45%, high LAD and LVDD had the highest plasma ANF and showed steady high plasma ANF for 15 days. Patients with EF greater than 45%, normal LAD and LVDD had elevated plasma levels only for 10 days, rising significantly on days 3-7 after admission. PRA and ADH values were normal throughout the study, whereas aldosterone was above the normal range only on admission. These findings suggest that the reduction in myocardial contractility induced by the infarction may account for the rise in ANF secretion via increased left atrial pressure or left atrial dilatation.

Effect of plasma volume expansion on hemodynamics and atrial natriuretic factor release in heart-transplant recipients

Plasma atrial natriuretic factor (ANF), plasma cyclic guanosine monophosphate (cGMP), plasma aldosterone, plasma-renin activity (PRA) and hemodynamic parameters were measured in heart-transplant recipients and control patients (chest pain syndrome) during right-sided heart catheterization under basal conditions and in response to an intravenous saline load. Basal plasma ANF and cGMP were higher in heart-transplant recipients than in control patients, whereas PRA and plasma aldosterone did not differ. The high plasma ANF levels in heart-transplant recipients did not result from high atrial pressures but appeared to be related with elevated atrial dimensions and cyclosporine-induced renal failure. During volume expansion, plasma ANF increased in control patients and remained elevated during the postinfusion period. In heart-transplant recipients, the changes in plasma ANF were less marked despite identical increases of atrial pressures. The sluggish response of plasma ANF in this group was associated in the postinfusion period with a nonreturn of the hemodynamic parameters to their basal values in contrast with what was observed in control patients.

Vasodilatory action of endogenous atrial natriuretic factor in a rat model of chronic heart failure as determined by monoclonal ANF antibody.

Elucidation of the role of (elevated) endogenous atrial natriuretic factor (ANF) in chronic heart failure has been hampered by a lack of specific inhibitors. We used a newly developed monoclonal antibody that has been shown to specifically block both exogenously and endogenously released ANF in vivo. For assessment of the vasodilatory action of ANF in chronic heart failure, either this antibody against ANF or ascites (control serum) was injected in rats with myocardial infarction and failure and in sham animals. Ascites did not alter central hemodynamics in either the sham or infarcted group. Antibody significantly increased right atrial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance (SVR) in the infarction group but did not affect these variables in the sham group. Because renal blood flow, as measured by radioactive microspheres, decreased significantly in all four groups, probably due to nonspecific renal vasoconstrictor effects of the ascites, a separate group of infarcted animals was treated with purified ANF antibody (devoid of nonspecific effects) or mouse IgG as a control injection. In these animals, right atrial pressure increased from 1.1 +/- 0.7 to 2.6 +/- 0.7 mm Hg (p less than 0.001). Although SVR, renal blood flow velocity (measured by Doppler probe), and renal vascular resistance did not change in the infarcted animals after administration of purified ANF antibody, a significant correlation was found between baseline plasma ANF values and the change in SVR exerted by purified ANF antibody (r = 0.758, p less than 0.02, n = 9); that is, SVR increased in rats with high baseline plasma ANF (greater than 350 pg/ml), but decreased in animals with plasma ANF less than 200 pg/ml. These results suggest that moderately elevated endogenous plasma ANF levels in chronic heart failure do affect central hemodynamics, primarily by reducing venous pressure (e.g., by decreasing intravascular volume or by venous dilation). Arterial vasodilation, however, appears to emerge when plasma ANF is greatly increased.

Effect of a chronic infusion of atrial natriuretic factor on glomerular and vascular receptors in spontaneously hypertensive rats

To investigate the effect of a prolonged infusion of atrial natriuretic factor (ANF) on its vascular and glomerular receptors, ANF (Ser 99-Tyr 126) was chronically administered (100 ng/h) for 7 days by osmotic minipumps to spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Blood pressure in the SHR fell from 149 +/- 5 to 119 +/- 3 mmHg 5 days after the ANF infusion was initiated, whereas no changes were observed in ANF-infused WKY rats. The SHR had higher plasma levels of both ANF (1-98) and (99-126) than the normotensive controls, but the ANF infusion did not modify these values in either group. Diuresis, natriuresis and haematocrit remained unchanged during the infusion. The higher plasma ANF levels noted in the SHR were associated with a decreased density (Bmax) and enhanced affinity (Kd) of ANF-binding sites in the mesenteric vessels. This pattern was not modified by the ANF infusion. The hypertensive animals had glomerular ANF receptors with a higher affinity than the WKY rats. The Bmax of these receptors was decreased significantly in ANF-infused SHR and WKY rats compared with non-infused animals. We conclude that the lack of change in vascular ANF receptors, during chronic ANF infusion in the SHR, could be associated with the hypotensive response.

Recruitment of the left ventricle for production of atrial natriuretic factor in Dahl salt-hypertension sensitive rats.

Dahl salt-sensitive (S) rats on normal salt intake develop a chronic form of hypertension with aging whereas Dahl salt-resistant (R) rats do not. In old hypertensive S rats the left ventricle is recruited for the production of ANF as evidenced by a seven- to ten-fold increase in atrial natriuretic factor (ANF) mRNA and increased ANF in ventricular tissue. Plasma ANF is also markedly increased in hypertensive S rats but there is no direct proof that ventricular production of ANF contributes to high plasma ANF. Atrial ANF is higher in S than R rats but this strain difference is not associated with strain differences in ANF mRNA in atria and atrial ANF mRNA does not increase dramatically in hypertensive S rats as does ventricular mRNA. Recruitment of the ventricle to produce ANF is clearly a secondary consequence of hypertension, but its functional significance is not established.

Atrial natriuretic factor in essential hypertension and adrenal disorders.

Patients with untreated essential hypertension had significantly higher plasma atrial natriuretic factor (ANF) levels (92.9 +/- 12.9 pg/ml, mean +/- SE) than those of age-matched controls (37.8 +/- 6.0 pg/ml; p less than 0.01). Plasma ANF levels in essential hypertensive patients showed a significant positive correlation with mean arterial pressure (MAP; r = 0.46, p less than 0.05) and an inverse correlation with plasma renin activity (PRA; r = -0.43, p less than 0.05). Plasma ANF levels after medication showed significant correlation with the decrease in MAP (r = 0.565, p less than 0.05). Patients with primary aldosteronism had significantly higher plasma ANF levels (122.4 +/- 30.2 pg/ml, n = 8) than those of controls (p less than 0.05). The levels returned to normal after extirpation of adrenal tumors. The response of plasma ANF levels in patients with primary aldosteronism to volume expansion with infusion of 2 L of physiological saline in 2 hours was greater than in controls. Such exaggerated response disappeared after surgical treatment. Infusion of angiotensin II (Ang II; 20 ng/kg/min) or norepinephrine (200 ng/kg/min) for 30 minutes to normal volunteers (n = 5) resulted in a rise in MAP (24.9 +/- 3.3 and 15.8 +/- 4.4 mm Hg, respectively) and a twofold increase in plasma ANF level. Infusion of the Ang II antagonist [Sar1, Ile8]Ang II (600 ng/kg/min) for 30 minutes, resulted in a rise in MAP (18.8 +/- 2.1 mm Hg) and more than a twofold increase in plasma ANF level in patients with essential hypertension (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)