Reciprocal interactions of neuropeptide y and angiotensin II receptors with a2-adrenoceptors in the nucleus tractus solitarii of the rat

Abstract: -Neuropeptide Y (NPY), angiotensin II (Ang II) and adrenergictransmission lines in the nucleus tractus solitarii (NTS), the major relay nucleusinvolved in the cardiovascular reflex, play an important role in centralcardiovascular control. The present work explored reciprocal interactions of NPYand Ang II receptor subtypes with a2-adrenoceptors in the NTS of thenormotensive Sprague-Dawley rat (SD), the normotensive Wistar Kyoto rat(WKY) and the spontaneously hypertensive rat (SHR) by using a cardiovascularanalysis, quantitative receptor autoradiography, immunocytochemistry and in situhybridization techniques. a2A-Adrenoceptors have been shown to be present in almost allcatecholaminergic neurons in the brainstem including the NTS. NPY Yl or AngII ATl receptor-like immunoreactivity (-LI) was found to be colocalized withtyrosine hydroxylase-LI in the NTS suggesting colocalization of these receptorswith a2-adrenoceptors in catecholaminergic neurons of the NTS. In the NTS of the SD, the NPY Yl and Y2 receptor agonists decreased theaffinity and transduction of a2-adrenoceptors. In contrast, a2-adrenoceptoragonists increased NPY Y2 receptor affinity but reduced the NPY Y2 receptorfunctions, i.e., the NPY Y2 receptor-mediated cardiovascular actions and theNPY-induced c-Fos expression in the NTS. NPY Y2 receptor agonists reducedtransduction over NPY Yl receptors in the NTS. In the SHR, a2A-adrenoceptor mRNA levels and a2-adrenoceptor bindingsites in the NTS were lower than those in the WKY. NPY in the NTS of the SHRhad an increased potency to antagonize a2-adrenoceptor function. This suggeststhat abnormal NPY/a2-adrenergic receptor interaction may contribute to thedevelopment of hypertension. In the NTS of the SD, activation of Ang II ATI receptors reduced theaffinity and transduction of a2-adrenoceptors, whereas a2-adrenoceptoractivation had the opposite effect on Ang II receptors. Ang II differentially regulates a2-adrenoceptors in the NTS of the WKYand the SHR. In the WKY, Ang II reduced the affinity and function of a2-adrenoceptors. In the SHR, however, Ang II increased them. This opposite effectin the SHR may be one compensatory mechanism to counteract the developmentof high blood pressure in the SHR. In conclusion, the present work provides evidence for reciprocalinteractions of NPY and Ang II receptors with a2-adrenoceptors in the NTSparticipating in cardiovascular regulation which are altered in relation tospontaneous hypertension.Keywords: Neuropeptide Y; angiotensin II; adrenaline; noradrenaline, clonidinereceptor; receptor-receptor interaction; cardiovascular control; immediate earlygene; microinjection; quantitative receptor autoradiography;immunocytochemistry; in situ hybridization(~) Shao-Nian Yang, 1996Printed in Sweden by Repro Print AB, StockholmISBN 91-628-1833-3