Dose-response study of atrial natriuretic peptide bolus injection in healthy man.
The effects of human atrial natriuretic peptide (ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by lithium clearance, and plasma levels of sodium and water homeostatic hormones were studied in a dose-response study with 50 healthy subjects. Placebo or ANP 0.5, 1.0, 1.5, or 2.0 micrograms kg-1 bwt was given as an intravenous bolus injection to five different groups. GFR rose after ANP, whereas no immediate change in RPF was observed. Significant increases with no distinct additional effect of ANP doses higher than 1.0 microgram kg-1 were detected in filtration fraction, urinary flow rate and urinary excretion rate of sodium. Both proximal and distal fractional reabsorption of sodium was reduced and the effect seemed to flatten out at doses higher than 1.0 microgram kg-1. Dose-dependent increases in cyclic guanosine monophosphate in urine and plasma were found after ANP bolus injection, and the rise in both was correlated with the increase in urinary sodium excretion. ANP caused a dose-dependent decrease in blood pressure and an increase in pulse rate. Plasma concentrations of angiotensin II and arginine vasopressin did not change after ANP. In summary, we found that ANP bolus injection caused a natriuresis and diuresis in healthy man with a threshold at a dose of 1.0 microgram kg-1. No distinct further renal effects were observed with higher doses despite dose-dependent increases in urinary cGMP excretion and plasma cGMP. Inhibition of both proximal and distal tubular fractional sodium reabsorption by ANP contributed to the natriuretic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine and Nephrology C, Skejby Hospital, University Hospital, Aarhus, Denmark.
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D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage* / Q000097:blood; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000097:blood; D012079:Renal Circulation / Q000187:drug effects
D000804:Angiotensin II; D001127:Arginine Vasopressin; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D011188:Potassium