Effects of atrial natriuretic factor in conscious rhesus monkeys with acute volume expansion.
The renal and hemodynamic responses to intravenous anaritide, a human atrial natriuretic factor [102-126] at 0.3 to 20 micrograms/kg in conscious rhesus monkeys with and without acute extracellular hypervolemia were analyzed and compared. Acute isotonic saline loading (intravenous bolus at 10 mL/kg plus continuous infusion at 0.25 mL/kg/min 30 min prior to and maintained throughout experiment) significantly augmented urine output (UV) and urinary Na+ excretion rate (UNaV) by 31% and 91%, respectively. Radial mean arterial pressure (MAP) and heart rate (HR) were not affected by volume expansion. Anaritide at doses higher than 0.3 micrograms/kg reduced MAP in a dose-dependent fashion in euvolemic monkeys. In contrast, reduction in MAP was observed only at the highest dose (20 micrograms/kg) of anaritide in hypervolemic monkeys. The hypotensive responses to anaritide at 20 micrograms/kg in euvolemic and hypervolemic animals were similar (-26 +/- 5 v -24 +/- 5 mm Hg, respective maximum changes in MAP). UV and UNaV were increased by anaritide at 3 to 20 micrograms/kg in both euvolemic and hypervolemic monkeys; however, the increases at each effective dose of anaritide were greater or tended to be greater in hypervolemic rhesus monkeys compared with euvolemic rhesus monkeys. Compared to vehicle responses, HR was not affected by anaritide in either group of animals. In conclusion, acute extracellular hypervolemia potentiates the renal but suppresses the hypotensive responses to anaritide in conscious rhesus monkeys.
Lee
K C
KC
Department of Experimental Therapeutics, Wyeth-Ayerst Research, Princeton, New Jersey.
Greenwood
J M
JM
Wendt
R L
RL
Lappe
R W
RW
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010953:Plasma Volume / Q000502:physiology*
D004232:Diuretics; D010446:Peptide Fragments; C042703:anaritide; D009320:Atrial Natriuretic Factor