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Hemodynamic actions of systemically injected pituitary adenylate cyclase activating polypeptide-27 in the ratThe aims of this study were (1) to characterize the hemodynamic mechanisms underlying the hypotensive effects of pituitary adenylate cyclase activating polypeptide-27 (PACAP-27 0.1-2.0 nmol/kg, i.v.) in pentobarbital-anesthetized rats, and (2) to determine the roles of the autonomic nervous system, adrenal catecholamines and endothelium-derived nitric oxide (NO) in the expression of PACAP-27-mediated effects on hemodynamic function. PACAP-27 produced dose-dependent decreases in mean arterial blood pressure and hindquarter and mesenteric vascular resistances in saline-treated rats. PACAP-27 also produced pronounced falls in mean arterial blood pressure in rats treated with the ganglion blocker, chlorisondamine (5 mg/kg, i.v.). The hypotensive and vasodilator actions of PACAP-27 were not attenuated by the beta-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.), or the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME 50 micromol/kg, i.v.). PACAP-27 produced dose-dependent increases in heart rate whereas the hypotensive response produced by the nitrovasodilator, sodium nitroprusside (10 microg/kg, i.v.), was associated with a minimal tachycardia. The PACAP-27-induced tachycardia was unaffected by chlorisondamine, but was virtually abolished by propranolol. These results suggest that the vasodilator effects of PACAP-27 are due to actions in the microcirculation rather than to the release of adrenal catecholamines and that this vasodilation may not involve the release of endothelium-derived NO. These results also suggest that PACAP-27 produces tachycardia by directly releasing norepinephrine from cardiac sympathetic nerve terminals rather than by direct or baroreceptor reflex-mediated increases in sympathetic nerve activity.
Document ID
20040142081
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Whalen, E. J.
(University of Iowa Iowa City 52242-1109, United States)
Johnson, A. K.
Lewis, S. J.
Date Acquired
August 22, 2013
Publication Date
January 22, 1999
Publication Information
Publication: European journal of pharmacology
Volume: 365
Issue: 3-Feb
ISSN: 0014-2999
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL-57472
CONTRACT_GRANT: HL-14388
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Regulatory Physiology

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