V. Da Cunha et al., Cyclooxygenase inhibition reduces blood pressure elevation and vascular reactivity dysfunction caused by inhibition of nitric oxide synthase in rats, CLIN EXP HY, 22(2), 2000, pp. 203-215
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.