Endothelium-dependent relaxation by alpha 2-adrenoceptor agonists in spontaneously hypertensive rat aorta.
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.
Sunano
S
S
Faculty of Pharmacological Sciences, Kinki University, Higashi-Osaka, Osaka, Japan.
Li-Bo
Z
Z
Matsuda
K
K
Sekiguchi
F
F
Watanabe
H
H
Shimamura
K
K
D000109:Acetylcholine / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D000068438:Brimonidine Tartrate; D004730:Endothelium, Vascular / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D019335:Nitroarginine; D000068438:Brimonidine Tartrate; D013928:Thromboxane A2; C037866:STA 2; D000109:Acetylcholine; D007213:Indomethacin