Abstract
The role of nitric oxide in the coronary vasodilation caused by acetylcholine or bradykinin in perfused guinea-pig hearts was investigated by using 1 mM L-NG-nitro arginine (L-NNA), a specific inhibitor of the formation of nitric oxide from L-arginine. L-NNA increased coronary perfusion pressure and inhibited the vasodilator responses to acetylcholine and bradykinin. The extent of vasodilation was evaluated in terms of the reduction of perfusion pressure from the initial baseline that had been induced by U-46619. L-NNA markedly attenuated coronary vasodilation caused by 5×10-11 mol of acetylcholine from 15±1 to 4±1 mmHg (p<0.01), and that caused by l×l0-11 mol bradykinin from 21±2 to 8±1 mmHg (p<0.01). On the other hand. L-NNA only weakly inhibited coronary vasodilation caused by 5×10-7mol of acetylcholine from 40±3 to 27±4 mmHg (p<0.01), and that caused by 1×10-9 mol of bradykinin (from 39±2 to 32±2 mmHg (p<0.01). L-NNA had no effect on the vasodilation induced by 1 × 10-8 mol of bradykinin. Ibuprofen, cyclooxygenase inhibi-tor, did not affect these vasodilatory responses. 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 responses to acetylcholine or bradykinin. Thus, nitric oxide is largely responsible for the vasodilatory responses to low doses of acetylcholine or bradykinin. However, mechanisms other than the release of nitric oxide or prostaglandins may be involved in the vasodilatory responses to high doses of acetylcholine or bradykinin.
