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Biomedical subjects

G Bönner

Publications and source records attributed to G Bönner.

At least 37 records · Page 2Linked to original sources
PubMed1994

Hyperinsulinemia, insulin resistance, and hypertension.

Obesity is the most common reason for insulin resistance with consequent hyperinsulinemia. Other reasons for hyperinsulinemia are type II diabetes mellitus and a genetic predisposition with a family history of hypertension. Hyperinsulinemia is considered to cause blood pressure elevation and is generally accepted as an independent risk factor for atherosclerosis. However, insulin per se does not elevate blood pressure, but rather reduces total peripheral vascular resistance in experimental studies. Blood pressure might be elevated by other mechanisms secondary to hyperinsulinemia, however, such as enhanced renal sodium retention, elevated intracellular free calcium, and increased activity of the sympathetic nervous system. Indeed, subjects whose blood pressure is salt-sensitive exhibit hyperinsulinemia after glucose loading, and normotensive subjects with glucose-induced hyperinsulinemia will develop hypertension within 5 years more often than normoinsulinemic subjects. In primary hypertension, the incidence of insulin resistance and hyperinsulinemia is much higher than in normotensive controls. However, not all reported studies show a relationship between hyperinsulinemia and blood pressure elevation, and in some experimental studies no blood pressure elevation could be induced by prolonged hyperinsulinemia. Therefore, it is still unclear whether hyperinsulinemia induces hypertension or is only casually associated with it. Nevertheless, treatment of hyperinsulinemia is recommended to avoid secondary complications. Treatment should begin with weight reduction and physical exercise, which will improve insulin resistance. Hypertension benefits more from weight reduction than from exercise. If drug therapy of hypertension is required, angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blockers are the drugs of first choice. In addition, beta-blockers and centrally acting drugs appear to be of certain benefit. However, diuretics must be used carefully, because they ameliorate insulin resistance, induce dyslipoproteinemia, and stimulate the sympathetic nervous system.

Adrenergic beta-Antagonists↗
PubMed1993

Therapeutic safety of perindopril in the treatment of mild hypertension with concomitant nephropathy.

Angiotensin-converting enzyme (ACE) inhibitors are well established antihypertensives. Their effect on kidney function, however, seems to depend on the pathophysiological mechanisms underlying the clinical symptoms. In one part of the Perindopril and Therapeutic Safety Study (PUTS) the effect of a 6-week treatment with placebo or 4 mg/d of perindopril (Coversum, CAS 82834-16-0) on kidney function and albuminuria was investigated in 56 hypertensives with concomitant nephropathy. The study was performed as multicenter, randomized, placebo-controlled, double-blind study. The results show that perindopril reduced blood pressure effectively. The responder rate determined as a fall in blood pressure at least about 10 mmHg in the perindopril group was 39% vs. 21% in the placebo group. All investigated parameters of kidney function like serum creatinine, creatinine clearance, urinary excretion of albumin and alpha 1-microglobulin remained unchanged during the study. In a subgroup of patients with isolated albuminuria ACE inhibition reduced significantly the urinary albumin excretion (perindopril: -292 +/- 205 mg/g creat. vs. placebo: +61 +/- 48 mg/g creat: p < 0.05). From this study it can be concluded that in hypertension with concomitant nephropathy, except renovascular hypertension and hypertension in renal transplant recipients, ACE inhibition by perindopril will not impair kidney function. In the early phase of nephropathy with isolated albuminuria and normal serum creatinine perindopril improves albuminuria and seems to be even of benefit for the kidney.

Adult↗
PubMed1992

[Does the captopril test improve the diagnosis of primary hyperaldosteronism?].

Plasma concentrations of renin and aldosterone were measured before and 60 min after taking 25 mg captopril in 242 patients with arterial hypertension (124 men, 118 women, aged 51.9 +/- 12.7 years; unilateral aldosterone-producing adrenal adenoma in 8, idiopathic hyperaldosteronism in 16 and essential hypertension in 189). Basal plasma aldosterone levels were twice as high in those with adenoma or hyperaldosteronism (216.9 +/- 99.1 pg/ml and 256 +/- 123 pg/ml, respectively) as in those with essential hypertension (117.7 +/- 115 pg/ml). Basal renin levels in adenoma and idiopathic hyperaldosteronism (1 +/- 0.8 microU/ml and 2.6 +/- 1.9 microU/ml, respectively) were decreased compared with those in essential hypertension (13.1 +/- 14.2 microU/ml). The basal aldosterone/renin ratio was higher in adenoma (436 +/- 370 pg/microU) and idiopathic hyperaldosteronism (615 +/- 950 pg/microU) than in essential hypertension (52.9 +/- 151.3 pg/microU). The sensitivity of this ratio in combination with the aldosterone concentration was 100% for recognizing an adrenal adenoma, its specificity 92.7%. The mean plasma aldosterone level after captopril administration did not change in adenoma patients, but fell to 162 +/- 85 pg/ml (P less than 0.001) in those with idiopathic hyperaldosteronism. These data indicate that the captopril test contributes to distinguishing primary from idiopathic hyperaldosteronism.

Adenoma↗
PubMed1992

Effect of bradykinin on arteries and veins in systemic and pulmonary circulation.

Bradykinin is a potent vasodilating and natriuretic peptide, which is potentiated by angiotensin-converting enzyme (ACE) inhibitors. In our investigations we studied the effect of bradykinin on systemic and pulmonary circulation as well as on dorsal hand vein tone. The effects of bradykinin on systemic and pulmonary circulation were tested by injection of bradykinin into the right atrium. Parameters were determined for blood pressure, cardiac output, ECG and mean pressure in pulmonary artery. Heart rate, total peripheral resistance, pulmonary vascular resistance, and pulmonary arteriolar resistance were calculated by these measured parameters. The data raised in our investigations showed clearly that bradykinin reduced blood pressure by reducing total peripheral vascular resistance in a dose-dependent manner. In pulmonary circulation bradykinin develops a direct effect. All circulatory actions of bradykinin are not mediated by prostaglandins, since inhibition of prostaglandin synthesis by indomethacin (100-150 mg) was without any effect. ACE inhibition by ramipril (5 mg) or captopril (50 mg) potentiated all effects of bradykinin about 20- to 50-fold, whereas it decreased angiotensin I effects only about four- to fivefold. These results suggest, that endogenous kinins, if they will be similarly potentiated by ACE inhibition like the exogenous bradykinin in our experiments, might play an important role in the blood pressure lowering effect of ACE inhibitors. Dorsal hand vein tone was reduced by bradykinin too, indicating that kinins can lower cardiac preload by increasing venous blood pooling.

Adult↗
PubMed1992

ACE inhibitor effect on bradykinin metabolism in the vascular wall.

In the isolated rabbit thoracic aorta the ACE inhibitor ramiprilat attenuated bradykinin degradation by enzymes localized on vascular endothelial cells as well as on vascular smooth muscle cells by 26% and 32%, respectively. We conclude that the ACE inhibitor can attenuate vascular bradykinin degradation not only by inhibition of endothelial ACE but also by inhibition of other bradykinin degrading enzymes in deeper layers of the vascular wall.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Lack of oral kallikrein in lowering systemic blood pressure in primary hypertension.

Primary hypertension is associated with a lack in renal kallikrein activity which might be one of the reasons for the blood pressure elevation. Some smaller and partially uncontrolled studies suggested that an oral substitution of glandular kallikrein lowers blood pressure by a kinin-mediated vasodilation and increased natriuresis. To test this hypothesis we treated in two studies over 100 patients with untreated mild to moderate primary hypertension (WHO I-II) for 5 resp. 12 weeks in a double blind randomized and placebo controlled manner with 1800 U glandular kallikrein orally. Blood pressure measurements were performed according to the two study designs after 3 and 5 resp. 8 and 12 weeks of treatment sphymomanometrically in the day time course. No significant changes in blood pressure by kallikrein treatment could be observed at any time. Neither renal kallikrein excretion, renin and ACE-activity nor blood glucose concentration in diabetics or non-diabetics was changed. Thus, we could undoubtedly demonstrate that oral applied glandular kallikrein has no effect on primary hypertension.

Administration, Oral↗
PubMed1991

[Effectiveness of pravastatin and bezafibrate in primary hypercholesterolemia].

The efficacy and safety of pravastatin and bezafibrate (in retard form) were compared in a randomised double-blind trial comprising 96 patients (48 men, 48 women; mean age 52.5 [20-68] years) with primary hypercholesterolaemia types IIa and IIb. After four weeks' treatment 6 out of 38 patients (400 mg/d bezafibrate) and 27 out of 58 patients (20 mg/d pravastatin) reached a LDL cholesterol level of 190 mg/dl or less. In the other 31 patients of the pravastatin group the dose was raised to 40 mg/d. During the twelve-week course of pravastatin total cholesterol concentration fell from a mean of 364 +/- 75 mg/dl (initial value) to 281 +/- 61 mg/dl (P less than 0.01), while LDL-cholesterol fell from 288 +/- 81 mg/dl to 206 +/- 64 mg/dl (P less than 0.01) and triglyceride concentration from 168 +/- 83 mg/dl to 148 +/- 80 mg/dl (P less than 0.05). During the twelve-week course of treatment with 400 mg bezafibrate total cholesterol concentration fell from a mean of 363 +/- 91 mg/dl to 325 +/- 73 mg/dl (P less than 0.01), LDL-cholesterol level fell from 284 +/- 88 mg/dl to 242 +/- 70 mg/dl (P less than 0.01) and the triglyceride concentration from 173 +/- 91 mg/dl to 121 +/- 83 mg/dl (P less than 0.01). HDL cholesterol concentration rose by 9% in the bezafibrate group and by 8.4% in the pravastatin group (P less than 0.05). Except in the case of HDL-cholesterol, the falls were significantly different in the two treatment groups: pravastatin was superior to bezafibrate in terms of the reductions in both total and LDL-cholesterol (P less than 0.01 for each). However, bezafibrate produced a greater fall in serum triglycerides (P less than 0.05). No serious side effects were associated with either drug.

Adult↗
PubMed1990

Converting enzyme inhibition and vascular prostacyclin synthesis: effect of kinin receptor antagonism.

The effects of angiotensin I-converting enzyme (ACE) inhibitors and bradykinin (BK) on prostacyclin (PGI2) production in isolated arterial tissue were investigated. Rings of rat abdominal aorta were incubated in Krebs-Ringer bicarbonate buffer and PGI2 generation was assessed by the determination of its stable hydrolysis product; 6-keto-PGF1 alpha. The addition of both ACE inhibitors, captopril and lisinopril, and bradykinin resulted in dose-dependent stimulation of PGI2 biosynthesis when the individual substance was added into the incubation buffer at final concentrations between 10(-8) and 10(-5) M. The bradykinin-induced stimulation of PGI2 synthesis was dose dependently inhibited by the BK receptor antagonist, D-Arg[Hyp3, Thi5,8, D-Phe7]BK. The captopril- and lisinopril-induced stimulation of vascular 6-keto-PGF1 alpha production was also significantly decreased when the BK antagonist was added to the incubation medium together with the ACE inhibitors. Our results show that both captopril and lisinopril stimulate PGI2 synthesis in arterial tissue and that this effect may be secondary to changes in the activity of the kinin system.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Converting enzyme inhibition in kinin-deficient brown Norway rats.

The contribution of endogenous kinins to the acute antihypertensive actions of the converting enzyme inhibitor ramipril was investigated in kinin-deficient Brown Norway rats and in Brown Norway-Hannover rats and Wistar rats as controls. In Brown Norway rats, urinary kinin excretion was measurable but extremely low when compared with control strains. The depressor responses to intra-arterial bradykinin injections 1) were not different between Brown Norway and Brown Norway-Hannover rats, 2) were potentiated by intravenous ramipril (60 micrograms), and 3) were attenuated by intra-arterial infusion of the bradykinin antagonist B4146 (40 micrograms/kg/min) to a similar extent in both strains. In renal hypertensive (two-kidney, one clip) Brown Norway rats, the blood pressure reductions to intravenous bolus injections of ramipril (100 micrograms) were significantly reduced both in extent and duration when compared with hypertensive Brown Norway-Hannover and Wistar rats. Intra-arterial infusion of B4146 (40 micrograms/kg/min) attenuated the depressor response to ramipril in Wistar and Brown Norway-Hannover rats but had no effect in Brown Norway rats. In contrast, all three groups showed similar depressor responses to intravenous infusions of the angiotensin II receptor antagonist saralasin. These responses were not influenced by the bradykinin antagonist. Our data support the hypothesis that kinins are important for the acute antihypertensive actions of converting enzyme inhibitors.

Angiotensin II↗
PubMed1990

Hemodynamic effects of bradykinin on systemic and pulmonary circulation in healthy and hypertensive humans.

In our studies, we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intra-arterially (40-6,050 pM/kg) and was infused intra-arterially (40-6,050 pM/kg/min). The investigations were performed in 21 normotensive and 15 hypertensive patients. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol of Na/day), salt loading (300 mmol of Na/day), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 X 1 mg), indomethacin (2 X 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure in a dose-related manner by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, beta-adrenoceptors, histamine-1 receptors, and prostaglandins. ACE inhibitors protentiate the blood pressure-lowering effect of bradykinin approximately 20- to 50-fold. In the case of intra-arterial injection of bradykinin, only 2-5% of the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From these experiments, a pulmonary clearance rate of bradykinin of over 95% can be calculated. In the pulmonary arteries, bradykinin has no effect on vascular resistance. In patients suffering from primary or renovascular hypertension, the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE inhibitors was not altered in the hypertensives. In patients suffering from borderline hypertension or primary hyperaldosteronism, bradykinin caused the same blood pressure lowering effect as in the normotensives.

Adult↗
PubMed1990

Kinin-related effects of angiotensin-converting enzyme inhibition.

Angiotensin-I-converting enzyme (ACE) converts angiotensin-I to angiotensin-II and splits bradykinin into inactive fragments. Inhibition of that enzyme attenuates kinin degradation and potentiates the action of kinins in many pharmacological investigations. Kinins are very potent vasodilating peptides which reduce blood pressure by lowering peripheral vascular resistance. Under experimental conditions in vitro kinins mediated a lot of metabolic and hemodynamic effects of the ACE inhibitors. However, it is still not known whether kinins also play a major role in the blood pressure-lowering effect of ACE inhibitors in vivo. New and highly specific assays are available to determine kinins in blood. But after ACE inhibition no homogeneous changes in circulating kinins are observed by reviewing recently published studies and even inhibition of kallikrein-kinin systems by either antibradykinin-antiserum or aprotinin does not clarify the role of kinins in the hemodynamic responses to ACE inhibition. The newly available bradykinin receptor antagonists inhibit in vitro and in vivo the effect of exogenous bradykinin. They were metabolized like kinins and in higher doses can develop kinin-like activities. After intravenous injection the bradykinin-receptor antagonists induce in vivo an increase in systemic blood pressure and thereby can reduce the blood pressure-lowering effect of ACE inhibitors markedly. However, it is unclear to date whether the bradykinin receptor antagonists developed their blood pressure-enhancing effect only by blocking the kinin-induced vasodilation or by some other stimulating effects on the vasopressor hormones. As long as the mechanisms of the hemodynamic action of the bradykinin antagonists are uncertain, no unequivocal interpretation of the results is possible and the role of kinins in the action of ACE inhibitors in vivo remains still uncertain.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Interference of different ACE-inhibitors with the diuretic action of furosemide and hydrochlorothiazide.

In healthy volunteers the acute effect of furosemide (40 mg i.v.) and hydrochlorothiazide (100 mg p.o.) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated. Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly probably due to a diminished (about 50%) proximal-tubular secretion of furosemide. Captopril did not alter significantly the furosemide induced changes in urinary kallikrein and kinin excretion. After captopril there was a clear dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. Other ACE-inhibitors like ramipril (5 mg) or enalapril (20 mg) did not influence the stimulatory effects of furosemide on diuresis or kallikrein-kinin excretion. Ramipril at a dose of 10 mg, however, enhanced the initial diuretic effect of furosemide by increased furosemide secretion and increased relative sodium excretion. Hydrochlorothiazide induced a prolonged diuresis which was not changed by either captopril or ramipril. Urinary kallikrein excretion was not stimulated by hydrochlorothiazide. Our results show an important drug interference between captopril and furosemide, which is independent of ACE-inhibition and probably only due to an interference in proximal-tubular secretion of both drugs. Between captopril and hydrochlorothiazide no such interaction could be observed.

Adult↗
PubMed1989

[Atrial natriuretic peptide and its significance for arterial hypertension].

Atrial natriuretic peptide is a recently discovered cardiac hormone with natriuretic, vasodilatory and hypotensive activities. The role of this hormone in the pathophysiology of hypertension is of particular interest. In contrast to an earlier concept, a deficiency of the atrial peptide could not be found in animal models of hypertension or in patients. ANP plasma levels were elevated in SHR with accelerated hypertension, in salt-sensitive Dahl rats, in rats with DOCA-salt-hypertension and in animals with renovascular hypertension. Elevated ANP levels under these conditions can be explained by an expansion of the intravascular volume or by an elevated atrial wall stretch induced by the hypertension itself. In patients with primary hypertension, plasma levels of the peptide are raised in some patients and are normal in others. Plasma ANP levels correlate with age, blood pressure and signs of left ventricular hypertrophy. A negative correlation is described between ANP and renin. Measurement of plasma ANP levels does not allow a differentiation between primary and secondary forms of hypertension. Elevated ANP levels are also found in primary hyperaldosteronism and in renal failure. Stimulation of ANP secretion by physical exercise and dietary salt loading is maintained in hypertension. Infusion of 1-28-hANP leads to a reduction in systemic arterial pressure in normotensives and hypertensives. The natriuresis induced by exogenous ANP is more pronounced in hypertensives. Stimulation of endogenous ANP secretion does not prevent the rise in blood pressure possibly due to a reduction in ANP receptors in target tissues.

Acromegaly↗
PubMed1989

[Effect of bradykinin on systemic and pulmonary hemodynamics in the human].

In our studies we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intraarterially (40-6050 pM/kg) respectively was infused intraarterially (40-6050 pM/kg/min). The investigations were performed in 21 normotensives and 15 hypertensives. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol Na/d), salt loading (300 mmol Na/d), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 x 1 mg), indomethacin (2 x 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure dose related by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, of beta adrenoceptors, of histamine-1 receptors, and of prostaglandins. ACE-inhibitors potentiate the blood pressure lowering effect of bradykinin about 20- to 50-fold. In case of an intraarterial injection of bradykinin in only 2-5% o the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From this experiments a pulmonary clearance rate of bradykinin over 95% can be calculated. In the pulmonary arteries bradykinin has no effect on the vascular resistance. In patients suffering from primary or renovascular hypertension the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE-inhibitors was not altered in the hypertensives. In patients suffering from bradykinin hypertension or primary hyperaldosteronism bradykinin developed the same blood pressure lowering effect as in the normotensives.

Adult↗
PubMed1989

Impact of acute and chronic sodium loading on atrial natriuretic peptide and renin in man.

The relationship between the renin-angiotensin system and the atrial natriuretic peptide and its contributions to the control of sodium balance is not clarified. We therefore studied plasma renin concentration (PRC) and plasma levels of atrial natriuretic peptide (ANP) in normal subjects during acute and chronic salt loading. Acute intravascular volume expansion by iv infusion of 2000 ml of normal saline resulted in sharp rise in plasma ANP from 122 +/- 24 to 405 +/- 141 pg/ml (p less than 0.05). This increase was only transient with plasma ANP returning to control levels after 240 min. In contrast, reduction in plasma renin concentration was less pronounced, however it was persistent for up to 240 min paralleled by a reduction in plasma protein. Reciprocal changes in ANP plasma levels and PRC were observed during dietary modification in sodium intake. At the end of low sodium diet over 4 days, supine plasma ANP averaged 49 +/- 7 pg/ml and levels increased to 128 +/- 38 pg/ml after 6 days of high sodium intake in 11 healthy subjects (p less than 0.05). In contrast, PRC values averaged 69.8 +/- 19.8 microU/ml and 14.4 +/- 6.5 microU/ml during low and high sodium diet respectively (p less than 0.01). The inverse relation between PRC and ANP was seen after prolonged dietary sodium loading over 15 days in 8 additional subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Renal and adrenal resistance against atrial natriuretic peptide in congestive heart failure: effect of angiotensin I-converting-enzyme inhibition.

We compared the natriuretic and diuretic effect of an intravenous infusion of 1-28 human atrial natriuretic peptide (hANP) (0.1 micrograms/kg/min over 30 min) in 10 patients with congestive heart failure (CHF) and in 10 control subjects of similar age and sex. In the controls, urine volume rose from 36.8 +/- 8.55 to 115.6 +/- 34.2 ml/30 min and urinary sodium excretion from 4.55 +/- 0.8 to 11.2 +/- 2.24 mEq/30 min before and during the infusion of ANP, respectively. In patients, baseline urine volume and sodium output were similar, however, rise in urine volume and urinary sodium was greatly reduced during the infusion of hANP. In patients with CHF, baseline plasma ANP levels (604.1 +/- 135.3 vs. 39.4 +/- 5.85 pg/ml; p less than 0.005) and urinary excretion of cyclic GMP (cGMP) (41.8 +/- 5.22 vs. 15.2 +/- 4.19 nmol/30 min; p less than 0.05) were significantly elevated compared to controls. The absolute and relative rise in cGMP excretion, however, was blunted in patients with CHF. In the controls, angiotensin I-converting-enzyme (ACE) inhibition by enalapril significantly reduced the urinary output of sodium and water after ANP infusion. Plasma ANP levels and urinary cGMP remained unaltered by ACE inhibition. Furthermore, treatment with enalapril resulted in a rise in renin and a drop in aldosterone levels. The reduction of plasma renin and serum aldosterone by ANP was maintained after ACE inhibition. In the patient group, administration of enalapril (3 X 2.5 mg every 6 h) reduced ACE activity in the serum from 84.7 +/- 16.9 to 2.13 +/- 0.88 U/l. Arterial blood pressure was lowered from 114.7 +/- 6.69 to 106.1 +/- 7.25 mm Hg systolic and from 76.9 +/- 3 to 69.2 +/- 3.7 mm Hg diastolic. However, natriuresis and diuresis and creatinine clearance following infusion of ANP remained unaltered.

Adrenal Glands↗
PubMed1989

Natriuretic action of ANP is blunted by ACE inhibition in humans.

We investigated the impact of angiotensin I-converting enzyme (ACE) inhibition by enalapril (3 X 2.5 mg p.o.) on the renal action of acute intravenous (i.v.) infusion of atrial natriuretic peptide (1-28-hANP 0.1 micrograms/kg/min for 30 min) in 10 normal subjects. During the control infusion of ANP, urinary sodium excretion rose from 4.5 +/- 0.8 to 11.2 +/- 2.2 mEq/min and urine volume from 32 +/- 14 to 115 +/- 34 ml/30 min. This increment in urinary volume and sodium output during ANP infusion was almost completely reduced by ACE inhibition. ANP plasma levels before and during the infusion and stimulation of urinary cGMP excretion were unaltered by ACE inhibition. However, enalapril treatment reduced systolic blood pressure (SBP) from 112 +/- 3 to 106 +/- 3 mm Hg and diastolic blood pressure (DBP) from 71 +/- 2 to 66 +/- 3 mm Hg. The small rise in glomerular filtration rate (GFR) during the control infusion of ANP was not observed after pretreatment with enalapril. The study demonstrates the importance of the renin-angiotensin system for the natriuretic and diuretic action of ANP in normal humans.

Adult↗