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

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

<P> 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 N<SUP>w</SUP>-nitro- L-arginine (L-NNA, 100 &#12557;M), methylene blue (10 &#12557;M) and LY83583 (10 &#12557;M), respectively. 3) Inhibition of cyclooxygenase with indomethacin (10 &#12557;M) strongly decreased the vasorelaxant response to AII irrespective of the presence of endothelium. 4) 7-Ethoxyresorufin (1 &#12557;M) and clotrimazole (1 &#12557;M), inhibitors of cytochrome P-450-dependent arachidonic acid metabolism, greatly attenuated the vasodilator response to AII. 5) Carbacyclin, arachidonic acid and prostaglandin F<SUB>2α</SUB> (PGF<SUB>2α</SUB>) caused concentration-dependent relaxations in the mesenteric artery with endothelium, which were inhibited by L-NNA and methylene blue. 6) AII and PGF<SUB>2α</SUB> 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 PGF<SUB>2α</SUB> and 6-keto PGF<SUB>1α</SUB> from the arterial segments with endothelium, which was inhibitable by indomethacin, but not by L-NNA. <P> 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.