Mechanisms Underlying Relaxations Caused by Angiotensin II and Its Analogs in Isolated Rabbit Mesenteric Artery

In the present study, we characterized the angiotensin II (AII)-induced relaxations in the phenylephrine-precontracted rabbit mesenteric arteries with endothelium. 1) AII-induced relaxation was consistently observed in the rabbit mesenteric arteries with and without endothelium, but not in the aortic segment with endothelium. 2) AII-induced endothelium-dependent relaxation was markedly inhibited by (L-NNA, ), methylene blue () and LY83583 (), respectively. 3) Inhibition of cyclooxygenase with indomethacin () strongly decreased the vasorelaxant response to AII irrespective of the presence of endothelium. 4) 7-Ethoxyresorufin () and clotrimazole (), inhibitors of cytochrome P-450-dependent arachidonic acid metabolism, greatly attenuated the vasodilator response to AII. 5) Carbacyclin, arachidonic acid and prostaglandin () caused concentration-dependent relaxations in the mesenteric artery with endothelium, which were inhibited by L-NNA and methylene blue. 6) AII and significantly stimulated cyclic GMP formation in the mesenteric arteries with endothelium, which was inhibited by L-NNA and methylene blue, respectively. 7) AII enhanced synthesis of and 6-keto from the arterial segments with endothelium, which was inhibitable by indomethacin, but not by L-NNA. In conclusion, the vasorelaxant responses to AII of the rabbit mesenteric artery with endothelium are subserved by arachidonic acid and its metabolites produced via activation of cyclooxygenase and cytochrome P-450 enzyme as well as by nitric oxide.