Cyclooxygenase inhibition reduces blood pressure elevation and vascular reactivity dysfunction caused by inhibition of nitric oxide synthase in rats

In the present study we investigated the role of cyclooxygenase (COX)-depen dent vasoconstrictors in the hypertension and altered vascular reactivity f ollowing prolonged nitric oxide (NO) synthase inhibition. Male Wistar rats (250-270g) were divided into four groups and treated for 7 days with Placeb o (control), L-NAME (48 mg/kg/day), indomethacin (4 mg/kg/day) and L-NAME i n combination with indomethacin. L-NAME treatment induced arterial hyperten sion, in vitro aortic hyperresponsiveness to phenylephrine, impaired vasodi latory response to acetylcholine and no significant change in response to s odium nitroprusside. Indomethacin co-treatment partially prevented blood pr essure elevation, restored responsiveness to phenylephrine and improved sen sitivity to acetylcholine. Indomethacin treatment alone did not modify bloo d pressure and aortic vascular reactivity. Both enhanced phenylphrine-induc ed contraction and impaired acetylcholine-evoked vasodilation induced by ac ute NO synthase inhibition with L-NAME (10(-4)M) in normal rat aortas were not modified by indomethacin (10(-5)M). These results are consistent with t he hypothesis that constricting factors, which arise from the COX pathway, contribute to hypertension and altered vascular reactivity following contin ued inhibition of NO synthase.