Peptide YY administration into the posterior hypothalamic nucleus of the rat evokes cardiovascular changes by non-adrenergic, non-cholinergic mechanisms.
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 alpha(1)-adrenoceptor antagonist prazosin (PRAZ, 0.2 mg kg(-1)); (iii) the V(1)-vasopressin receptor antagonist [d(CH(2))(5)Tyr(Me)]AVP (AVPX, 20 microg kg(-1)); (iv) the combination of AVPX, PENT and MeATR; (v) the combination of PRAZ, AVPX, PENT, MeATR, and the alpha(2)-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-naive 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 Y(1) 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.
Martin
J R
JR
Department of Pharmacology, A.T. Still University of Health Sciences, Kirksville College of Osteopathic Medicine, 800 W. Jefferson Street, Kirksville, MO 63501, USA.
D000311:Adrenal Glands / Q000294:innervation / Q000502:physiology; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007034:Hypothalamus, Posterior / Q000502:physiology*; D008845:Microinjections; D010276:Parasympatholytics / Q000008:administration & dosage / Q000494:pharmacology; D010277:Parasympathomimetics / Q000008:administration & dosage / Q000494:pharmacology; D019894:Peptide YY / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013153:Splanchnic Nerves / Q000502:physiology; D013238:Stereotaxic Techniques
D010276:Parasympatholytics; D010277:Parasympathomimetics; D019894:Peptide YY