ENDOTHELIUM-DEPENDENT RELAXATION BY ALPHA(2)-ADRENOCEPTOR AGONISTS INSPONTANEOUSLY HYPERTENSIVE RAT AORTA

Differences in alpha(2)-adrenoceptor-induced relaxation of the aorta b etween stroke-prone spontaneously hypertensive rats (SHRSP) and contro l normotensive Wistar Kyoto rats (WKY) were studied. Changes in the te nsion of ring preparations of the aortas were measured isometrically. Relaxation was observed in the preparations precontracted in the prese nce of ONO-11113. a thromboxane A(2) analogue. The alpha(2)-agonist cl onidine and UK-14304 induced dose-dependent relaxation in both the WKY and HRP preparations. The relaxation was impaired in the SHRSP prepar ation. A modified sandwich experiment showed that the relaxing substan ce from the SHRSP endothelium was decreased. Acetylcholine (ACh) also induced dose-dependent relaxation, and the relaxation was impaired in the SHRSP preparations. alpha(2)-Agonists induced a greater degree of impairment in the relaxation than did ACh. The relaxation induced by a lpha(2)-agonists and by ACh was blocked by N-G-nitro-L-arginine (L-NNA ). Indomethacin improved the relaxation induced by ACh but not that in duced by alpha(2)-agonisrs in the SHRSP aortas. These results suggest that the impairment of relaxation by alpha(2)-agonists in SHRSP is not caused by the increase in the release of endothelium-derived contract ing factor (EDCF) but by the reduction in the release of nitric oxide (NO). Alteration of the alpha(2)-adrenoceptors and/or the intracellula r mechanism through which NO is synthesized by stimulation of the alph a(2)-adrenoceptors may be the cause of the reduction in relaxation.