ROLE OF NITRIC-OXIDE IN THE VASODILATORY RESPONSES TO ACETYLCHOLINE AND BRADYKININ IN PERFUSED HEARTS

The role of nitric oxide in the coronary vasodilation caused by acetyl choline or bradykinin in perfused guinea-pig hearts was investigated b y using 1 mM L-N(G)-nitro arginine (L-NNA), a specific inhibitor of th e formation of nitric oxide from L-arginine. L-NNA increased coronary perfusion pressure and inhibited the vasodilator responses to acetylch oline and bradykinin. The extent of vasodilation was evaluated in term s of the reduction of perfusion pressure from the initial baseline tha t had been induced by U-46619. L-NNA markedly attenuated coronary vaso dilation caused by 5 x 10(-11) mol of acetylcholine from 15 +/- 1 to 4 +/-1 mmHg (p<0.01), and that caused by 1 x 10(-11) mol bradykinin from 21+/-2 to 8+/-1 mmHg (p<0.01). On the other hand, L-NNA only weakly i nhibited coronary vasodilation caused by 5 x 10(-7) mol of acetylcholi ne from 40+/-3 to 27+/-4 mmHg (p<0.01), and that caused by 1 x 10(-9) mol of bradykinin (from 39+/-2 to 32+/-2 mmHg (p<0.01). L-NNA had no e ffect on the vasodilation induced by 1 X 10(-8) Mol of bradykinin. Ibu profen, cyclooxygenase inhibitor, did not affect these vasodilatory re sponses. These results suggest that the formation of nitric oxide from L-arginine in coronary resistance vessels helps to regulate vascular tone, and that prostaglandins are not related to the vasodilatory resp onses to acetylcholine or bradykinin. Thus, nitric oxide is largely re sponsible for the vasodilatory responses to low doses of acetylcholine or bradykinin. However, mechanisms other than the release of nitric o xide or prostaglandins may be involved in the vasodilatory responses t o high doses of acetylcholine or bradykinin.