Atrial natriuretic factor-induced systemic vasoconstriction in conscious dogs, rats, and monkeys.
This study addresses the hypothesis that atrial natriuretic factor (ANF) is a primary vasodilator, which reduces arterial pressure directly and increases total peripheral resistance secondarily by reflex mechanisms. The effects of 30-minute infusions of ANF (0.3 micrograms/kg/min i.v.) were examined in conscious dogs, rats, and monkeys before and after ganglionic blockade with hexamethonium. In seven intact, conscious dogs, ANF reduced mean arterial pressure by 7 +/- 1% and cardiac output by 19 +/- 3% and increased total peripheral resistance by 15 +/- 3%. After ganglionic blockade, ANF reduced mean arterial pressure by 7 +/- 2% but still increased total peripheral resistance by 15 +/- 3%. Similar results were observed in four dogs with total cardiac denervation and in six dogs with arterial baroreceptor denervation. Furthermore, in two dogs, combined ganglionic and alpha 1-adrenoceptor blockades failed to alter the rise in total peripheral resistance observed with ANF. In six intact, conscious rats, ANF reduced mean arterial pressure by 8 +/- 2% and cardiac output by 27 +/- 2% and increased total peripheral resistance by 27 +/- 5%. After ganglionic blockade, ANF still increased total peripheral resistance by 13 +/- 3%. In six intact, conscious monkeys, ANF reduced mean arterial pressure by 14 +/- 2% and cardiac output by 26 +/- 3% and increased total peripheral resistance by 17 +/- 3%. However, after ganglionic blockade. ANF decreased total peripheral resistance by 11 +/- 2%. These data provide evidence for a fundamental species difference in the vascular actions of ANF. In conscious dogs, ANF elicits "direct" vasoconstriction, which increases total peripheral resistance, even in the presence of denervation of reflexes or autonomic blockade. In conscious rats, ANF elicits both direct and reflexly mediated vasoconstriction. In conscious monkeys, although a component of direct vasoconstriction may also be present, the most prominent component appears to be reflexly mediated, since it was abolished by ganglionic blockade.
Shen
Y T
YT
Department of Medicine, Harvard Medical School, Brigham and Women's and Massachusetts General Hospital, Boston.
Young
M A
MA
Ohanian
J
J
Graham
R M
RM
Vatner
S F
SF
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D003243:Consciousness; D004285:Dogs / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D008251:Macaca / Q000502:physiology*; D008252:Macaca fascicularis / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats / Q000502:physiology*; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*; D014667:Vasopressins / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D014667:Vasopressins; D006830:Hydralazine; D009320:Atrial Natriuretic Factor; D012083:Renin; D005996:Nitroglycerin; D011224:Prazosin