sta-2 and Hypertension

Differences in alpha(2)-adrenoceptor-induced relaxation of the aorta between stroke-prone spontaneously hypertensive rats (SHRSP) and control normotensive Wistar Kyoto rats (WKY) were studied. Changes in the tension of ring preparations of the aortas were measured isometrically. Relaxation was observed in the preparations precontracted in the presence of ONO-11113, a thromboxane A(2) analogue. The alpha(2)-agonist clonidine and UK-14304 induced dose-dependent relaxation in both the WKY and SHRSP preparations. The relaxation was impaired in the SHRSP preparation. A modified sandwich experiment showed that the relaxing substance 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 alpha(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 induced by alpha(2)-agonists 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 contracting factor (EDCF) but by the reduction in the release of nitric oxide (NO). Alteration of the alpha(2)-adrenoceptors and/or the intracellular mechanism through which NO is synthesized by stimulation of the alpha(2)-adrenoceptors may be the cause of the reduction in relaxation.

Topics: Acetylcholine; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Animals; Aorta; Brimonidine Tartrate; Endothelium, Vascular; Hypertension; Indomethacin; Nitroarginine; Quinoxalines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thromboxane A2; Vasodilation

We examined vascular thromboxane A2 (TXA2) generation and its relation to a proliferation of vascular smooth muscle cells (VSMCs) in spontaneously hypertensive rats (SHRs). Aortic TXA2 release was significantly enhanced in 5-week-old SHRs, as compared with Wistar-Kyoto strain rats (WKY). The cultured VSMCs of SHRs exhibited a shorter doubling time and a greater [3H]thymidine uptake than those of WKY rats. OKY 046 a thromboxane synthetase inhibitor, tempered proliferation of VSMCs in SHRs, but not in WKY rats. STA2, a stable analog of TXA2, stimulated VSMC growth in WKY rats more than in SHRs. It is indicated that vascular TXA2 generation is enhanced, and partially participates in the rapid proliferation of VSMCs in SHRs.

Topics: Animals; Blood Vessels; Cell Division; Hypertension; In Vitro Techniques; Methacrylates; Muscle, Smooth, Vascular; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thromboxane A2; Thromboxane-A Synthase