Infusion Of alpha-hANP Research Articles

Effect of chronic central alpha-hANP administration on blood pressure, water and electrolyte balance in rats.

Relatively few studies have evaluated the chronic effects of atrial natriuretic polypeptide (ANP) administration into the central nervous system on peripheral cardiovascular and renal function under conditions of expanded extracellular fluid volume. The present investigation examined the effects of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) chronically infused into the cerebroventriculum of rats loaded with 0.9% saline. Measurements of the arterial blood pressure, water and electrolyte balances were carried out during a 4-day central ventricular infusion of alpha-hANP. Significant increases in daily urine volume and urinary sodium and chloride excretion were observed, but no changes of arterial blood pressure occurred. These results indicate that elevated levels of ANP in the CSF can influence sodium and water excretion, but do not appear to influence arterial pressure.

Effects of alpha-human natriuretic peptide on renal hemodynamics and diuresis in dogs and perfused rat kidneys.

Effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on renal function were studied in anesthetized dogs and isolated perfused rat kidneys. Two doses of alpha-hANP were used to determine whether renal hemodynamics or tubular reabsorption is tha major factor in the diuretic action of alpha hANP. The excretion rates of sodium (Na) and inorganic phosphate (PO4) were evaluated to determine the site of diuretic action in the renal tubule. In dogs that received the smaller dose of alpha-hANP (5 ng.kg-1.min-1) infused into the renal arteries without changes in systemic or renal hemodynamics, urine volume (UV) and urinary Na excretion (UNaV) increased significantly. Fractional excretion of Na (FENa) was increased, while fractional excretion of PO4 (FEpo4) was unchanged, following the infusion of alpha-hANP. The calculated fractional Na reabsorption in the distal tubule (DTRNa) during the infusion of alpha-hANP was significantly suppressed. In dogs that received the a larger dose of alpha-hANP (50 ng.kg-1.min-1), the glomerular filtration rate (GFR), UV, and FENa were increased and DTRNa was decreased. In isolated rat kidneys perfused at a constant pressure, a lower concentration of alpha-hANP (0.5 ng.ml-1) in the perfusate caused diuresis and increased Na and PO4 excretion without any renal hemodynamic alterations. A higher concentration of alpha-hANP (5 ng.ml-1) increased GFR, Na and PO4 excretion. Since PO4 reabsorption is believed to occur primarily in the renal proximal tubule, these findings suggest that the diuretic action of alpha-hANP in smaller doses in induced by direct action on renal distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal renal sensitivity to atrial natriuretic peptide in Gordon's syndrome.

To test the hypothesis that renal sensitivity to atrial natriuretic peptide (ANP) is impaired in Gordon's syndrome (hypertension and hyperkalaemia with normal glomerular filtration rate) we infused alpha-hANP into two patients with this syndrome (a sister and a brother, 19 and 18 years of age). For comparison, 11 healthy volunteers were also examined. The infusion of alpha-hANP increased urinary volume and excretion of sodium similarly in the patients and controls. The excretion of potassium did not change in either the patients or the controls. The infusion of alpha-hANP had no effect on the serum potassium levels or the plasma CO2 content in the patients. The present results do not confirm the hypothesis of lack of sensitivity to ANP as a pathophysiological concept in Gordon's syndrome.

Regional blood flow effects of ANP in conscious dogs: preferential gastrointestinal vasoconstriction

We studied total and regional blood flow responses to human atrial natriuretic peptide (alpha-hANP) using radioactive microspheres in six conscious dogs. Hemodynamic responses to infusions of alpha-hANP at 75 ng.kg-1.min-1 were determined in each dog in the presence and absence of autonomic reflexes using the ganglion blocking agent pentolinium. When autonomic reflexes were blocked, alpha-hANP caused a substantial reduction in gastrointestinal (GI) vascular conductance (35%) but had no significant effects in brain, kidneys, liver, skeletal muscle, or skin. This alpha-hANP-induced fall in GI conductance contributed more than 40% to the fall in total peripheral conductance (TPC) of 24% occurring after autonomic blockade. A fall in myocardial vascular conductance, most prominent in the left ventricle, contributed a further 40% to the fall in TPC. When autonomic reflexes were intact, alpha-hANP caused vasoconstriction in the GI region (29% fall in vascular conductance), had no significant effects on myocardial vascular conductance but significantly increased splenic vascular conductance. In addition to these systemic responses, alpha-hANP infusion also significantly reduced pulmonary vascular conductance, independent of autonomic reflex activity or changes in pulmonary artery pressure. Thus our results in conscious dogs demonstrate that alpha-hANP causes a systemic vasoconstriction, most pronounced in the GI region.

Effects of atrial natriuretic peptide on systemic and renal hemodynamics and renal excretory function in patients with chronic renal failure.

We examined the effects of 60 min alpha-hANP infusion (24 ng/min/kg) on glomerular filtration rate (GFR), renal blood flow (RBF), cardiac index (CI) and blood pressure (BP) in 8 patients with chronic renal failure (CRF) with GFR ranging from 18 to 80 ml/min/1.73 m2 and in 8 control (C) subjects with normal renal function. Basal plasma levels of ANP and cGMP were elevated in CRF (ANP: 60.6 +/- 9.1 vs 13.6 +/- 1.9 pmol/l, p less than 0.05; cGMP: 14.3 +/- 2.9 vs 6.6 +/- 1.1 pmol/ml, p less than 0.05). During ANP infusion, peak levels of cGMP were higher in CRF than in C (27.5 +/- 3.2 vs. 17.3 +/- 1.3 pmol/ml, p less than 0.05). During ANP infusion, GFR increased in CRF by 70.7 +/- 4.2% from 34.5 +/- 6.8 to 57.4 +/- 9.9 ml/min/1.73 m2 (p less than 0.001) as compared to 16.2 +/- 1.4% in C (p less than 0.001 vs CRF). RBF increased in CRF by 43.6 +/- 6.4% and in C by 3.1 +/- 1.2% (p less than 0.01). Basal urinary sodium excretion (UNaV) was slightly lower in CRF than in C but rose to the same level in both groups during ANP infusion. In CRF, as opposed to C, UNaV remained elevated above baseline after the end of the infusion. The effect of ANP on fractional sodium excretion (FENa), however, was more pronounced in C.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide in patients with essential hypertension. Hemodynamic, renal, and hormonal responses.

In six patients with essential hypertension (EH) and in six healthy volunteers (C) the effects of a 60-min intravenous (iv) infusion of human atrial natriuretic peptide (alpha-hANP) (24 ng/min/kg) on systemic and renal hemodynamics and renal excretory function were evaluated. Basal plasma ANP concentrations in patients with EH were higher (P less than .05) than in C (30.9 +/- 4.5 v14.0 +/- 1.7 pmol/L). Maximal effects of alpha-hANP infusion occurred after 30 to 60 min. Blood pressure (BP) declined from 154 +/- 5/109 +/- 4 to 139 +/- 7/94 +/- 4 in EH and from 117 +/- 1/72 +/- 2 to 106 +/- 1/65 +/- 3 mm Hg in C (P less than .05). Cardiac output (CO) increased transiently from 6.1 +/- 0.3 to 6.5 +/- 0.4 L/min in EH and from 6.8 +/- 0.3 to 7.2 +/- 0.5 L/min in C, whereas heart rate (HR) remained constant both in patients with EH and in C (69 +/- 3 to 72 +/- 5 and 60 +/- 3 to 63 +/- 3/min). The increases in urine flow and in urinary sodium excretion from 3.6 +/- 0.2 to 16.0 +/- 2.0 mL/min and from 230 +/- 33 to 1004 +/- 137 mumol/min, respectively, in EH were more pronounced than in C (from 3.9 +/- 1.0 to 8.4 +/- 0.8 mL/min and from 211 +/- 37 to 451 +/- 84 mumol/min); (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

On the role of neural mechanisms in the cardiocirculatory inhibitory action of ??-human atrial natriuretic peptide in the anesthetized rabbit

The effects induced by alpha-human 28-amino acid residue atrial natriuretic peptide (alpha-hANP) on arterial pressure, heart rate and vascular resistance, measured as hindlimb perfusion pressure (HPP), were examined in anesthetized rabbits. In particular, the involvement of the autonomic nervous system in mediating the cardiocirculatory effects of alpha-hANP was investigated. Intravenous alpha-hANP (8 micrograms/kg, bolus injection) in anesthetized rabbits caused a sustained decrease in atrial pressure, a transient decrease in HPP and no significant changes in heart rate. After sinoaortic denervation, alpha-hANP produced a greater decrease in arterial pressure and in hindlimb vascular resistance and also a consistent decrease in heart rate. Bilateral vagotomy did not significantly alter the cardiocirculatory responses to alpha-hANP in either normal or in sinoaortic denervated rabbits. Intravenous infusion of alpha-hANP (2 micrograms/kg bolus + 0.2 micrograms/kg per min) did not substantially change the baroreflex cardiocirculatory responses to loading and unloading carotid and aortic baroreceptors with bilateral carotid occlusion and phenylephrine or nitroglycerin bolus injection. In addition, alpha-hANP infusion did not modify the cardiovascular reflex responses to chemical stimulation of neural receptors (sensory endings of group III and IV somatic afferents) in the hindlimb muscles which are primarily mediated by sympathetic nerves in the anesthetized rabbit. Pharmacological blockade of the autonomic nervous system with atropine and guanethidine did not reduce the hypotensive and bradycardic effects caused by alpha-hANP in sinoaortic denervated animals. The results indicate that in anesthetized rabbits: (1) alpha-hANP can induce inhibitory cardiocirculatory responses (hypotension, bradycardia, musculocutaneous vasodilation) which are consistently offset by the sinoaortic baroreceptor system; (2) alpha-hANP does not alter the reflex control of arterial pressure and heart rate by arterial baroreceptors and muscle chemosensitive receptors; (3) activation of cardiopulmonary vagally-mediated depressor reflexes does not contribute to the inhibitory cardiovascular action of alpha-hANP; and (4) inhibitory effects on sympathetic activity do not constitute a significant component of the cardiocirculatory action of alpha-hANP.

Atrial Natriuretic Peptide in Patients With Diabetes Mellitus Type I: Effects on Systemic and Renal Hemodynamics and Renal Excretory Function

In the present study the effects of 1 h intravenous infusion of alpha-human atrial natriuretic peptide (24 ng/min/kg) on systemic and renal hemodynamics and on renal excretory function were studied in six insulin-treated and metabolically well-controlled patients with diabetes mellitus (DM) type I and in six healthy control subjects (C). Basal plasma atrial natriuretic peptide (ANP) concentration was 14.6 +/- 2.0 in DM patients and 14.9 +/- 1.3 pmol/L in C and rose similarly in both groups to 87.1 +/- 22.1 and to 86.9 +/- 11.1 pmol/L, respectively, during alpha-hANP infusion (P less than .05). Maximal effects of alpha-hANP occurred between 30 and 60 min after the start of the infusion. Mean arterial pressure (MAP) (83 +/- 5 v 81 +/- 3 mm Hg), heart rate (HR) (63 +/- 2 v 64 +/- 4/min) and total peripheral resistance (TPR) (11 +/- 1 v 10 +/- 1 mm Hg.min/L) remained unaltered in patients with DM. In contrast, in C MAP and TPR decreased from 83 +/- 3 to 77 +/- 2 mm Hg and from 12 +/- 1 to 10 +/- 1 1 mm Hg.min/L, respectively (P less than .05), whereas HR increased from 53 +/- 2 to 59 +/- 3 beats/min (P less than .05). Cardiac output (CO) rose initially by 11% and by 9% in DM and C, respectively. Urine flow increased from 4.1 +/- 0.9 to 11.3 +/- 1.5 mL/min in DM patients and from 3.9 +/- 1.0 to 8.4 +/- 0.8 mL/min in C (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Different effects of α-human atrial natriuretic peptide and nitroglycerin on cardiac dimensions in humans

This study aimed to examine whether alpha-human atrial natriuretic peptide (alpha-hANP) alters cardiac dimensions in humans. Left atrial (LA) and left ventricular diastolic (LV) diameters were measured by echocardiography at control and with lower body negative pressure (LBNP) at -10 and -20 mmHg during intravenous (IV) infusion of saline or alpha-hANP at a dose of 0.03-0.04 microgram/kg per minute (n = 8). Studies were also done during IV infusion of saline or nitroglycerin (NG) at a dose of 10-15 micrograms/kg per minute in another group of subjects (n = 6). LBNP decreased central venous pressure (CVP) and the LA and LV diameter. alpha-hANP lowered CVP at rest and with LBNP at -10 and -20 mmHg compared with corresponding values during saline infusion; NG produced comparable decreases in CVP, which suggests that decreases in venous return caused by the two drugs were similar. However, NG decreased, but alpha-hANP did not alter the LA and LV diameter at rest or with LBNP. In another group of subjects (n = 4), we observed that alpha-hANP caused comparable decreases in CVP and pulmonary capillary wedge pressure. These data suggest that ANP may dilate the cardiac chambers in humans.

Pentobarbital anesthesia alters renal actions of alpha-hANP in dogs

The magnitude of the natriuretic response to an infusion of alpha-human atrial natriuretic peptide (alpha-hANP) has varied considerably in different studies. The greatest renal responses to alpha-hANP infusion have been observed in barbiturate-anesthetized dogs. We therefore examined the renal, hormonal, and cardiovascular responses to alpha-hANP infusion in eight female dogs, once awake and again anesthetized with pentobarbital sodium (25 mg/kg body wt). After a 20-min control period, alpha-hANP was infused at a rate of 25 ng.kg-1.min-1 for 60 min. In dogs when awake, infusion of alpha-hANP produced a significant increase in sodium excretion from a control value of 39 +/- 7 to 73 +/- 13 and 89 +/- 15 mu eq/min after 40 and 60 min. In dogs when anesthetized, infusion of alpha-hANP produced an increase in sodium excretion from 21 +/- 3 to 105 +/- 12 and 143 +/- 21 mu eq/min after 40 and 60 min. The increase in sodium excretion was significantly greater in dogs when anesthetized than when awake. We also investigated the role of the renal sympathetic nerves on these responses in six dogs after chronic bilateral renal denervation. In dogs with denervated kidneys when awake, infusion of alpha-hANP did not change sodium excretion significantly. In dogs with denervated kidneys when anesthetized, infusion of alpha-hANP significantly increased sodium excretion; however, the increase was significantly attenuated when compared with anesthetized dogs with intact kidneys. We conclude that the natriuretic response to an infusion of alpha-hANP is enhanced in dogs when anesthetized. Also, the natriuretic response was attenuated by renal denervation in dogs when anesthetized.

The Significance of cGMP and Dopamine Receptor on the Natriuretic and Hypotensive Activities of Synthetic Atrial Natriuretic Polypeptide in Essential Hypertension

This study was undertaken to clarify the role of dopamine receptor (DA2) on the effects of atrial natriuretic polypeptide(ANP) on blood pressure, plasma and urinary cyclic GMP, and urinary sodium excretion, alpha-human ANP (alpha-hANP) was intravenously administrated to 7 normal subjects and 14 patients with essential hypertension as follows: first a dose of 0.01 micrograms/kg/min for 30 minutes, and then 0.03 micrograms/kg/min with or without metoclopramide(MC) for 30 minutes. After the infusion of the 0.03 micrograms/kg/min dose of alpha-hANP, systolic blood pressure fell from 115 +/- 17 mmHg to 109 +/- 15 mmHg in normal subjects, and fell significantly from 163 +/- 33 mmHg to 145 +/- 26 mmHg in patients with essential hypertension. Diastolic blood pressure fell from 101 +/- 14 mmHg to 92 +/- 7 mmHg in patients with essential hypertension but did not change in normal subjects. A dose of 0.03 micrograms/kg/min of alpha-hANP led to a threefold rise in urine volume and twofold rise in urinary sodium excretion in normal subjects, and a fivefold rise in urine volume and fourfold rise in urinary sodium excretion in patients with essential hypertension. However, there was no relationship between the hypotensive and natriuretic effects of alpha-hANP in either normal subjects or patients with essential hypertensions. The infusion of a 0.03 micrograms/kg/min dose of alpha-hANP increased plasma cyclic GMP concentration from 4.1 +/- 2.1 pmol/ml to 34.3 +/- 25.Opmol/ml in normal subjects and from 4.5 +/- 2.6 pmol/ml to 20.3 +/- 7.4 pmol/ml in patients with essential hypertension. The rise in plasma cyclic GMP by alpha-hANP was suppressed by MC both in normal subjects and patients with essential hypertension. Urinary cyclic GMP excretion also increased during the infusion of alpha-hANP, but this effect was not suppressed by MC. Furthermore, plasma aldosterone concentration (PAC), which was depressed by alpha-hANP in normal subjects and patients with essential hypertension, was increased by MC. These results suggest that the hypotensive effect of alpha-hANP may depend not only on the natriuretic effect, but also on vasodilatation, the inhibition of aldosterone production or the suppression of the sympathoadrenomedullary system. Cyclic GMP may be produced through the DA2 receptor in vascular tissue but not in the kidney.

Cardiovascular, renal and endocrine effects of ??-human atrial natriuretic peptide in patients with Cushing??s syndrome and primary aldosteronism

The pharmacological effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) in patients with Cushing's syndrome and primary aldosteronism were compared with those in normal volunteers. An infusion of synthetic alpha-hANP at 0.1 microgram/kg per min for 20 min produced a maximal plasma hANP level of 800-1200 pg/ml in patients with Cushing's syndrome and primary aldosteronism, and in normal subjects. There were significant decreases in the mean blood pressure (-10 to -15 mmHg) in patients with Cushing's syndrome and primary aldosteronism, similar to those in normal subjects. The plasma cyclic 3'5'-guanosine monophosphate (cGMP) concentrations of both groups of patients were increased fivefold over the baseline level following the infusion. Infusion of synthetic alpha-hANP caused a greater increase in the rate of sodium excretion in patients with Cushing's syndrome and primary aldosteronism compared with normal volunteers. The plasma cortisol and aldosterone concentrations did not, however, significantly change during alpha-hANP infusion in either the patients with Cushing's syndrome or those with primary aldosteronism. As synthetic alpha-hANP has a potent hypotensive effect in hypertensive patients with Cushing's syndrome and primary aldosteronism, a significant reduction in blood pressure and natriuresis seems to occur without affecting adrenocortical steroidogenesis.

Plasma concentration and renal effect of human atrial natriuretic peptide in nephrotic syndrome.

To elucidate the pathophysiological role of atrial natriuretic peptide (ANP) in nephrotic syndrome, the plasma level of ANP and renal response to exogenous human alpha-ANP (alpha-hANP) were measured in untreated adult patients with idiopathic nephrotic syndrome (NS) and compared with those of normal volunteers (NL). The plasma concentration of immunoreactive ANP (ir-ANP) in NS (112 +/- 9.8 pg/ml, n = 9, mean +/- SE) was not significantly different from that in NL (98 +/- 8.0 pg/ml, n = 13). However, a significant positive correlation was observed between the plasma ir-ANP level and blood volume in NS (r = 0.714, p less than 0.05). In an infusion study with synthetic alpha-hANP (25 to 100 ng/kg/min), the urine flow rate increased from 0.67 +/- 0.08 to 7.11 +/- 1.08 ml/min in NL (n = 5, p less than 0.01) and from 0.64 +/- 0.16 to 2.88 +/- 0.70 ml/min in NS (n = 9, p less than 0.05) and the urinary sodium excretion increased from 115 +/- 16 to 466 +/- 62 microEq/min in NL (p less than 0.01) and from 51 +/- 8 to 207 +/- 58 microEq/min in NS (p less than 0.01). The absolute and percent changes in urine flow rate and the absolute change in sodium excretion were lower in NS (p less than 0.05) than in NL. The percent change in sodium excretion in NS did not differ from that in NL. In 2 patients with high plasma ir-ANP concentrations, however, infusion of ANP induced poor sodium excretion (59 and 95 microEq/min at 100 ng/kg/min ANP infusion, respectively). Hemodynamic and renal parameters such as blood pressure, pulse rate and creatinine clearance were similarly affected in both NL and NS. We also found that the urinary excretion of protein was significantly increased in NS (p less than 0.05) during infusion of alpha-hANP. Our data suggest that the plasma level of ir-ANP is regulated by blood volume status, and that the renal responsiveness to ANP, at least in part, contributes to water and sodium retention in NS.

Atrial natriuretic polypeptide(ANP) as protective agent of renal ischemia.

The effect of atrial natriuretic polypeptide (ANP) on hemodynamics and renal function was evaluated after the reconstructive surgery of the left renal artery in a patient with renovascular hypertension secondary to Takayasu's arteritis. The reconstructive surgery was done using the femoral artery, since we were unable to obtain adequate vein segments to fit the renal artery. The femoral artery was reconstructed by her saphenous vein segments. After 30 min of the aortorenal bypass operation, alpha-human ANP (alpha-hANP) was infused intravenously for 10 min at a rate of 0.1 microgram/kg/min. Although total peripheral resistance was decreased by alpha-hANP infusion, blood pressure was not changed because of the increased cardiac output. Glomerular filtration rate was increased markedly with concomitant increase in urine volume and urinary excretions of sodium, potassium and phosphate. Fractional excretions of water and sodium were not changed, but fractional excretion of phosphate and potassium clearance were increased. Thus, the infusion of alpha-hANP markedly improved the renal function of the ischemic kidney by the reconstructive surgery of the renal artery, suggesting that alpha-hANP seems clinically applicable as a protective agent in renal ischemia at renovascular surgery as well as the renal transplantation.

Effects of alpha-human atrial natriuretic peptide on the interrelationship of arterial pressure, aortic nerve activity, and aortic diameter.

A previous study has suggested that atrial natriuretic peptide (ANP) alters arterial baroreflex control of lumbar and renal sympathetic nerve activity. To explore these mechanisms, we examined the interrelationship of arterial pressure, afferent aortic nerve activity, and aortic diameter in rabbits anesthetized with alpha-chloralose before and after sinoaortic denervation and bilateral vagotomy. Arterial pressure was decreased in stepwise fashion by intravenous infusion of alpha-human ANP (alpha-hANP, 0.1-1.0 microgram/kg/min) or sodium nitroprusside (SNP, 1-5 micrograms/kg/min). Both in rabbits with intact baroreceptors and in those with baroreceptors denervated, aortic nerve activity and the aortic diameter decreased during hypotension caused by the infusion of SNP but remained unchanged during hypotension caused by the infusion of alpha-hANP. In addition, we examined the effects of alpha-hANP and SNP on the responses of the aortic diameter and aortic nerve activity to rapid changes in arterial pressure caused by intravenous phenylephrine or nitroglycerin. Changes in aortic nerve activity and the aortic diameter in response to rapid changes in arterial pressure caused by phenylephrine or nitroglycerin were not different between the infusion of alpha-hANP and SNP. These results suggest that aortic nerve activity remains unchanged despite hypotension during the infusion of alpha-hANP, because alpha-hANP dilates the aorta. Since the aortic diameter increases, strain of aortic baroreceptors does not decrease. A second suggestion is that alpha-hANP does not alter aortic baroreceptor responses to changes in arterial pressure caused by phenylephrine or nitroglycerin.

Natriuresis during atrial distension and a concurrent decline in plasma atriopeptin.

In the conscious dog, left atrial distension elicits a composite response that modulates both cardiovascular and renal function. The response to atrial distension may be mediated by the combined effects of neural reflexes and the release of atriopeptin. To assess the relative contributions of atrial reflex mechanisms and circulating atriopeptin to the renal response elicited by atrial distension, alpha-human atrial natriuretic peptide (alpha-hANP) was infused into conscious dogs at 50 ng.kg-1.min-1 for 60 min. Then the infusion was stopped abruptly, and left atrial pressure was increased 8 mmHg by inflating a balloon positioned above the mitral valve. Plasma atriopeptin decreased during the 40-min period of atrial distension, but urine flow and sodium excretion increased during this time. In another series of experiments, volume expansion was substituted for atrial distension. Saline (24 ml/kg) was infused intravenously for 5 min immediately after the 60-min period of alpha-hANP infusion. Urine flow and sodium excretion increased after administration of saline even though plasma atriopeptin decreased substantially during the same time period. These results provide evidence that circulating levels of atriopeptin do not play a dominant role in influencing sodium excretion either during atrial distension or in response to saline infusion.

Hemodynamic Effects of α-Human Atrial Natriuretic Peptide in Healthy Volunteers

The hemodynamic effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) were evaluated in a double-blind, placebo-controlled study with echocardiography and systolic time intervals in 11 healthy volunteers. During an infusion of alpha-hANP for 30 min, when plasma ANP concentration increased to a peak level of approximately 300 pg/ml, an increase occurred in diuresis (+174%, p less than 0.01 vs. placebo) and natriuresis (+148%, p less than 0.05). Heart rate increased (+10%, p less than 0.05), but the mean arterial pressure remained unchanged. The left ventricular end-diastolic diameter was reduced (-3%, p less than 0.01), as was the left ventricular end-systolic diameter (-11%, p less than 0.001). Total peripheral resistance (-12%, p less than 0.05) and midsystolic circumferential wall stress (-16%, p less than 0.05) decreased, while cardiac output increased (+15%, p less than 0.05), as did fractional shortening (+15%, p less than 0.001). Within 30 min postinfusion, all differences between the ANP and placebo treatments had disappeared. No significant difference between the treatments was observed in preejection period or preejection period/left ventricular ejection time ratio. In conclusion, when administered as a short infusion, alpha-hANP causes peripheral arterial vasodilation and thus, by reducing left ventricular afterload, improves the pump function of the heart. Venous vasodilating effect of alpha-hANP may contribute to the decrease in left ventricular preload, but a diuresis-induced reduction in circulating intravascular volume may also be influenced.

Plasma concentration of alpha-hANP and renal responses to alpha-hANP infusion in patients with congestive heart failure and those with chronic renal failure.

To study the role of alpha-human atrial natriuretic polypeptide (alpha-hANP) in body fluid regulation, we measured the plasma concentration of alpha-hANP and renal function in 9 patients with congestive heart failure (CHF), 10 with chronic renal failure (CRF) and 8 normotensives (NT) before and during alpha-hANP infusion at 0.025 microgram/kg.min. The plasma concentration of alpha-hANP was significantly higher in the CHFs and CRFs than in the NTs (319, 168 and 72 pg/ml, respectively). Alpha-hANP infusion decreased mean blood pressure in a similar manner in the 3 groups (-5%, p less than 0.01 each). Increases in urinary sodium excretion and glomerular filtration rate during alpha-hANP infusion, however, were greater in the CHFs and CRFs than in the NTs. Furthermore, the higher the preinfusion level of renal vascular resistance (RVR), the greater was the reduction in RVR by alpha-hANP (r = -0.80, p less than 0.001). The metabolic clearance rate (MCR) of alpha-hANP was significantly smaller in the CHFs and CRFs than in the NTs (38, 35 and 67 ml/min.kg, respectively). These results suggest that the renal vasodilatory actions of alpha-hANP seem to be enhanced in patients with increased RVR and that the elevation of the basal plasma concentration of alpha-hANP in CHFs and CRFs may be in part due to the low MCR.

Atrial natriuretic peptide protects against acute ischemic renal failure in the rat.

Because of its ability to increase glomerular filtration, antagonize the actions of vasoconstrictors, and produce vasodilation, alpha human atrial natriuretic peptide (alpha-hANP) was evaluated for its potentially beneficial effects in experimental ischemic renal failure induced by 45-60 min of renal artery occlusion in bilaterally or unilaterally renally intact Sprague-Dawley rats. After ischemia, a 4-h intrarenal infusion of alpha-hANP restored 14C-inulin clearances in bilaterally and unilaterally intact animals from 0.05 +/- 0.006 and 0.05 +/- 0.01 ml/min per 100 g to 0.314 +/- 0.04 and 0.25 +/- 0.01 ml/min per 100 g, respectively (P less than 0.001, n = 8), compared with normal values of 0.49 +/- 0.023 ml/min per 100 g. Histologically, there was a progressive decrease in medullary hyperemia and prevention of intratubular cell shedding and granulocyte margination as a result of the 4-h alpha-hANP infusion such that after 24 and 48 h the histological appearance of the tissue was essentially normal. The results show that a 4-h intrarenal infusion of alpha-hANP after renal ischemia can preserve glomerular filtration rate and reduce renal tissue damage.

Attenuation of reflex forearm vasoconstriction by alpha-human atrial natriuretic peptide in men.

This study examined whether atrial natriuretic peptide (ANP) modulates reflex forearm vasoconstriction in humans. Synthetic alpha-human ANP (alpha-hANP) was infused at a rate of 0.03 microgram/kg/min in 8 healthy men (mean age 23 +/- 0.7 years, mean +/- SEM). The alpha-hANP decreased systolic blood pressure and central venous pressure (CVP) but did not significantly alter resting heart rate and forearm vascular resistance (FVR). The magnitudes of reflex increases in FVR during lower body negative pressure (LBNP) at -110, -20, and -40 mm Hg were less during infusion of alpha-ANP than those magnitudes during infusion of saline solution. The slope of the regression line relating changes in CVP and those in FVR was less during infusion of alpha-hANP than the slope during infusion of saline solution. Forearm vascular responses to intra-arterial infusion of norepinephrine at doses of 100, 200, and 500 ng/min did not significantly differ during infusion of alpha-hANP and saline solution. These results suggest that alpha-hANP attenuates cardiopulmonary baroreflex control of FVR in normal men.