INCREASED POTENCY OF NEUROPEPTIDE-Y TO ANTAGONIZE ALPHA(2)-ADRENOCEPTOR FUNCTION IN THE NUCLEUS-TRACTUS-SOLITARII OF THE SPONTANEOUSLY HYPERTENSIVE RAT

The regulation by neuropeptide Y of alpha(2)-adrenoceptors in the nucl eus tractus solitarii was evaluated in the adult normotensive Wistar K yoto rat and the adult spontaneously hypertensive rat. The microinject ion of a submaximal dose of l-noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii produced a significant reduction in the mean arterial blood pressure in either strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1-36) for the vasodepressor respo nse in the Wistar Kyoto rat was five times higher than that (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore, neuropep tide Y(1-36) at 0.2 pmol in 50 nl could significantly counteract the v asodepressor response to l-noradrenaline (800 pmol in 50 nl) in the sp ontaneously hypertensive rat, but not in the Wistar Kyoto rat, in whic h 1 pmol in 50 nl of neuropeptide Y(1-36) must be employed to countera ct the vasodepressor response to l-noradrenaine (800 pmol in 50 nl), a lthough the vasodepressor responses are of a similar magnitude. The il l situ hybridization and quantitative receptor autoradiographical expe riments showed that the alpha(2A)-adrenoceptor messenger RNA levels an d the B-max value of the alpha(2)-adrenoceptor agonist [H-3]p-aminoclo nidine 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 res ults were consistent with the cardiovascular results and showed that i n the spontaneously hypertensive rat, neuropeptide Y(1-36) at 1 nM led to a significant increase in the K-d value of [H-3]p-aminocionidine b inding sites. In the Wistar Kyoto rat, neuropeptide Y(1-36) produced t his effect only at 10 nM. The present study provides evidence for an i ncrease of the potency of neuropeptide Y(1-36) to antagonistically mod ulate alpha(2)-adrenoceptors in the nucleus tractus solitarii of the s pontaneously hypertensive rat. This enhanced antagonistic action may p artly be related to a reduction in the number of alpha(2A)-adrenocepto rs in the nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease has been observed in the alpha(2A)-adrenoceptor messenger RNA levels and the alpha(2)-adrenoceptor binding sites in th e spontaneously hypertensive rat. This increased potency of neuropepti de Y(1-36) to antagonize alpha(2)-adrenoceptor function in the nucleus tractus solitarii of the spontaneously hypertensive rat may contribut e to the development of high blood pressure in this hypertensive strai n. (C) 1997 IBRO.