Increased potency of neuropeptide y to antagonize α2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat

Abstract

The regulation by neuropeptide Y of α2-adrenoceptors in the nucleus tractus solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult spontaneously hypertensive rat. The microinjection of a submaximal dose of l-noradrenaline (800pmol in 50nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1pmol in 50nl) of neuropeptide Y(1–36) for the vasodepressor response in the Wistar Kyoto rat was five times higher than that (0.2pmol in 50nl) in the spontaneously hypertensive rat. Furthermore, neuropeptide Y(1–36) at 0.2pmol in 50nl could significantly counteract the vasodepressor response to l-noradrenaline (800pmol in 50nl) in the spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1pmol in 50nl of neuropeptide Y(1–36) must be employed to counteract the vasodepressor response to l-noradrenaline (800pmol in 50nl), although the vasodepressor responses are of a similar magnitude. The in situ hybridization and quantitative receptor autoradiographical experiments showed that the α2A-adrenoceptor messenger RNA levels and the Bmax value of the α2-adrenoceptor agonist [3H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of the spontaneously hypertensive rat were substantially lower than those in the Wistar Kyoto rat. The quantitative receptor autoradiographical results were consistent with the cardiovascular results and showed that in the spontaneously hypertensive rat, neuropeptide Y(1–36) at 1nM led to a significant increase in the Kd value of [3H]p-aminoclonidine binding sites. In the Wistar Kyoto rat, neuropeptide Y(1–36) produced this effect only at 10nM. The present study provides evidence for an increase of the potency of neuropeptide Y(1–36) to antagonistically modulate α2-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat. This enhanced antagonistic action may partly be related to a reduction in the number of α2A-adrenoceptors in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the α2A-adrenoceptor messenger RNA levels and the α2-adrenoceptor binding sites in the spontaneously hypertensive rat.This increased potency of neuropeptide Y(1–36) to antagonize α2-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to the development of high blood pressure in this hypertensive strain.