EVIDENCE FOR A DIFFERENTIAL MODULATION OF THE ALPHA-2-ADRENOCEPTORS BY ANGIOTENSIN-II IN THE NUCLEUS-TRACTUS-SOLITARII OF THE SPONTANEOUSLYHYPERTENSIVE AND THE WISTAR-KYOTO NORMOTENSIVE RATS

An interaction between angiotensin II (Ang II) receptors and alpha(2)- adrenoceptors was evaluated in the nucleus tractus solitarii (NTS) of the normotensive Wistar-Kyoto rat (WKY) and of the spontaneously hyper tensive rat (SHR) using quantitative receptor autoradiography and card iovascular analysis. In the WKY rat, Ang II promoted a dose-dependent increase in the IC50 value of l-noradrenaline when competing for [H-3] p-aminoclonidine ([H-3]PAC) binding sites, which reached a maximum of 400% with 10 nM of Aug II and was associated with a small decrease in the B-0 value (20%). In the SHR Ang II (0.1 nM) had an opposite effect leading to a decrease in the IC50 value of about 57%, and no change w as observed in the B-0 value. Saturation analysis also showed that Ang II (0.1 nM) increased the K-D value of [H-3]PAC in the WKY strain but in contrast decreased the K-D value of [H-3]PAC in the SHR. The B-max value was not significantly changed neither in the WKY rat nor in the SHR. The cardiovascular analysis showed that a threshold dose of Ang II (0.05 pmol) counteracted the vasodepressor effect produced by l-nor adrenaline coinjected in the NTS of the WKY rat. No effect was observe d in heart rate. In the SHR no counteraction of the l-noradrenaline-in duced vasodepressor effect was found, and in contrast a slight increas e of the vasodepressor effect associated with a significant increase i n the bradycardiac response was observed. The results give evidence fo r an antagonistic Ang II/alpha(2) receptor interaction in the cardiova scular part of the NTS of the WKY rat as previously observed in the Sp rague-Dawley rat. However, this interaction is altered in the SHR, so that in this strain the Ang II/alpha(2) receptor interaction enhances alpha affinity and possibly alpha(2) receptor function. This opposite effect observed in the SHR may represent one compensatory mechanism to counteract the development of high blood pressure in the SHR.