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

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Abstract:

Summary

1 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.

2 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 V1-vasopressin receptor antagonist [d(CH2)5Tyr(Me)]AVP (AVPX, 20 g 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).

3 Adrenal demedullation inhibited the PYY-evoked responses of drug-na├»ve rats, and rats pretreated with the combination of PENT, MeATR and AVPX.

4 Transection of the splanchnic nerve innervating the adrenal medullae attenuated the bradycardia, as did ZD 7155, but not the PYY-evoked pressor response.

5 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.

6 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.

Keywords: adrenal demedullation; receptor subtypes; splanchnic nerve transection; sympatholytics

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1474-8673.2004.00331.x

Publication date: April 1, 2005

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