Involvement of thromboxane A2 in the mediation of the contractile effect induced by inhibition of nitric oxide synthesis in isolated rat middle cerebral arteries

Inhibition of nitric oxide (NO) synthesis induces vasoconstriction and reduction of the blood flow in the brain, indicating that basal release of NO provides a resting vasorelaxant tone in the cerebral circulation. In the present study, the contractile effect of the NO synthase blocker N-G-nitro-L-arginine (100 mu mol/L) in isolated rat middle cerebral arteries was attenuated markedly in the presence of the cyclooxygenase inhibitor indomethacin (5 mu mol/L), the thromboxane A(2) synthase inhibitor ridogrel (10 mu mol/L), or the thromboxane receptor antagonist ICI 192605 (100 mu mol/L). These results indicate that removal of the endogenous NO stimulates the release of thromboxane A(2) in cerebral vessels and basal NO production regulates the resting cerebrovascular tone, at least in part, by suppressing thromboxane A(2).