ALTERATION OF RESPONSE TO NEUROPEPTIDE-Y IN THE NUCLEUS-TRACTUS-SOLITARIUS OF SPONTANEOUSLY HYPERTENSIVE RATS

In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 pmo l) into the unilateral nucleus tractus solitarius elicited dose-depend ent vasodepressor and bradycardic responses accompanied by an inhibiti on of sympathetic nerve firing. After microinjections of the alpha(2)- adrenergic receptor antagonist yohimbine (100 ng) into the nucleus tra ctus solitarius, the depressor and bradycardic responses to the inject ion of neuropeptide Y (25 pmol) into the nucleus tractus solitarius we re significantly attenuated. In contrast, pretreatment with the alpha( 1)-adrenergic receptor antagonist doxazosin (200 ng) injected into the nucleus tractus solitarius did not alter these responses. In spontane ously hypertensive rats, microinjections of neuropeptide Y (25 pmol) i nto the nucleus tractus solitarius also elicited depressor and bradyca rdic responses that were significantly less than those of normotensive Wistar-Kyoto rats. However, pretreatment with yohimbine (100 ng) in t he nucleus tractus solitarius did not diminish these depressor respons es in spontaneously hypertensive rats. Depressor responses to neuropep tide Y, which was administered after yohimbine pretreatment, were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. Th e results suggest that the depressor and bradycardic responses elicite d by neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity. These responses may be mediated in part by alpha(2)-ad renergic receptor in the nucleus tractus solitarius. The impairment of alpha(2)-adrenergic receptor-mediated responses to neuropeptide Y in spontaneously hypertensive rats may contribute to the development of h ypertension.