Journal article
Hemodynamic actions of systemically injected pituitary adenylate cyclase activating polypeptide-27 in the rat
European journal of pharmacology, Vol.365(2), pp.205-215
1999
DOI: 10.1016/S0014-2999(98)00852-8
PMID: 9988104
Abstract
The 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 β-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.), or the NO synthase inhibitor,
N
G-nitro-
l-arginine methyl ester (
l-NAME 50 μmol/kg, i.v.). PACAP-27 produced dose-dependent increases in heart rate whereas the hypotensive response produced by the nitrovasodilator, sodium nitroprusside (10 μg/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.
Details
- Title: Subtitle
- Hemodynamic actions of systemically injected pituitary adenylate cyclase activating polypeptide-27 in the rat
- Creators
- Erin J Whalen - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USAAlan Kim Johnson - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USAStephen J Lewis - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA
- Resource Type
- Journal article
- Publication Details
- European journal of pharmacology, Vol.365(2), pp.205-215
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S0014-2999(98)00852-8
- PMID
- 9988104
- ISSN
- 0014-2999
- eISSN
- 1879-0712
- Language
- English
- Date published
- 1999
- Academic Unit
- Psychological and Brain Sciences; Neuroscience and Pharmacology; Health and Human Physiology
- Record Identifier
- 9984213263202771
Metrics
4 Record Views