Effects and pharmacokinetics of bolus injections of atrial natriuretic factor in normal volunteers.
The aim of this study was to examine the hemodynamic, renal, and endocrine effects of exogenous human atrial natriuretic factor (ANF), together with its pharmacokinetics, in healthy volunteers. Ten subjects participated in this study, in which the effects of a single bolus dose of ANF and of a matched vehicle injection were compared under a 135 mmol/day sodium intake. Doses of 3, 12.5, and 25 micrograms of ANF were given to 1 subject each, and doses of 50 and 100 micrograms were given to 4 and 3 subjects, respectively. Significantly, hemodynamic changes occurred at the 100 micrograms dose, when mean blood pressure decreased by 15% and heart rate increased reciprocally. Diuresis and natriuresis tended to increase following 50 micrograms but increased significantly and in a prolonged fashion following 100 micrograms of ANF. Atrial natriuretic factor did not cause significant changes in plasma catecholamine, renin activity, and aldosterone levels at any dose, although aldosterone tended to decrease. Plasma arginine-vasopressin concentrations decreased significantly following 100 micrograms. Plasma cyclic GMP levels increased in all subjects and in a dose-dependent fashion. Plasma ANF concentrations peaked 3-5 min following the bolus injection and returned toward baseline values within 10-60 min. Although with doses of less than or equal to 50 micrograms plasma ANF levels increased up to 8 to 50-fold, compared to baseline values, the only significant change was the increase in plasma cyclic GMP levels, perhaps because the effects of ANF were successfully masked by counter-regulatory mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Cusson
J R
JR
Clinical Research Institute of Montréal, Hôtel-Dieu de Montréal Hospital, Canada.
Du Souich
P
P
Hamet
P
P
Schiffrin
E L
EL
Kuchel
O
O
Tremblay
J
J
Cantin
M
M
Genest
J
J
Larochelle
P
P
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004231:Diuresis / Q000187:drug effects; D004702:Endocrine Glands / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007267:Injections; D008297:Male; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood
D009320:Atrial Natriuretic Factor; D012964:Sodium; D003404:Creatinine; D006152:Cyclic GMP; D011188:Potassium