Direct and neurohumoral cardiovascular effects of atrial natriuretic peptide.
We studied the hemodynamic changes produced in conscious, chronically instrumented rabbits during steady-state administration of atrial natriuretic peptide (ANP). We administered synthetic alpha-human ANP intravenously (i.v.) at progressively increasing doses of 1, 2, and 4 micrograms/min, each for 30 min. In different experiments in each rabbit, we determined the effects of the peptide under closed-loop conditions in the intact animal and the "direct" circulatory effects of the peptide after "total" blockade of the autonomic nervous system (TAB) and after combined neurohumoral blockade (NHB), where in addition the vascular effects of vasopressin and angiotensin II were also prevented. In intact rabbits, ANP produced a dose-related reduction in mean arterial pressure (MAP, -3 to -14%), which was entirely due to a fall in cardiac output (CO, -14 to -20%), and there was a small rise in total peripheral resistance (TPR 5-12%). Heart rate remained unchanged. In rabbits subjected to TAB and NHB, all hemodynamic effects of ANP were attenuated. There were dose-related falls in left and right atrial pressures which reached maxima of -3.3 +/- 0.9 and -1.8 +/- 0.2 mm Hg, respectively. There was a reversible rise in hematocrit, probably owing to a shift of approximately 8% in blood volume. These effects occurred mainly through direct actions of the peptide, and there was no evidence of systemic vasodilatation. The magnitude of reflex autonomic effects appeared to be less than expected for the observed fall in MAP, suggesting that ANP also inhibited cardiovascular reflexes.
Woods
R L
RL
Baker Medical Research Institute, Melbourne, Australia.
Oliver
J R
JR
Korner
P I
PI
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001337:Autonomic Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005730:Ganglionic Blockers / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology
D001337:Autonomic Agents; D005730:Ganglionic Blockers; D018377:Neurotransmitter Agents; D014667:Vasopressins; D000804:Angiotensin II; D008464:Mecamylamine; D009320:Atrial Natriuretic Factor