Peptide YY administration into the posterior hypothalamic nucleus of the rat evokes cardiovascular changes by non-adrenergic, non-cholinergic mechanisms

Document Type

Article

Publication Title

Autonomic and Autacoid Pharmacology

Abstract

Microinjection of peptide YY (PYY) (0.23-2.3 nmol) into the posterior hypothalamic nucleus (PHN) of conscious rats evokes a dose-dependent pressor response and a bradycardia. The increase in mean arterial pressure evoked by 2.3 nmol of PYY was not blocked by intravenous pretreatment with: (i) the nicotinic ganglionic receptor antagonist pentolinium (PENT, 10 mg kg-1) alone, or in combination with the muscarinic receptor antagonist methylatropine (MeATR, 1 mg kg-1); (ii) the α1-adrenoceptor antagonist prazosin (PRAZ, 0.2 mg kg-1); (iii) the V 1-vasopressin receptor antagonist [d(CH2) 5Tyr(Me)]AVP (AVPX, 20 μg kg-1); (iv) the combination of AVPX, PENT and MeATR; (v) the combination of PRAZ, AVPX, PENT, MeATR, and the α2-adrenoceptor antagonist yohimbine (0.3 mg kg-1); or (vi) the angiotensin II type 1 receptor antagonist ZD 7155 (1 mg kg -1). Adrenal demedullation inhibited the PYY-evoked responses of drug-naïve rats, and rats pretreated with the combination of PENT, MeATR and AVPX. Transection of the splanchnic nerve innervating the adrenal medullae attenuated the bradycardia, as did ZD 7155, but not the PYY-evoked pressor response. Systemic pretreatment of rats with the neuropeptide Y1 receptor antagonist BIBP 3226 (1 mg kg-1) blocked the PYY-evoked cardiovascular changes, but not those evoked by microinjection of carbachol (5.5 nmol) into the PHN. These results suggest that the cardiovascular changes evoked from the PHN by PYY requires the presence of the adrenal medullae, which are stimulated by: (i) a hormone to release an NPY-like substance that evokes the pressor response, and (ii) the splanchnic nerve to evoke the release of a substance that results in the bradycardia. © 2005 Blackwell Publishing Ltd.

First Page

53

Last Page

67

DOI

10.1111/j.1474-8673.2004.00331.x

Publication Date

4-1-2005

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