Cerebral vasospasm: effects of prostaglandin synthetase inhibitors in vitro

Because previous studies suggest that prostaglandins (PGs) are involved in the contraction of cerebral arteries, the present study was undertaken to assess the direct effects of arachidonic acid, the precursor of PGs, on isolated dog basilar arteries and to ascertain the actions of three prostaglandin synthesis inhibitors, aspirin, indomethacin, and meclofenamate, on contractions induced by agonists of diverse chemical structure. Arachidonic acid induced sustained contractions and in optimal concentrations produced constriction that was 56% as great as that produced by serotonin. These responses were markedly inhibited (95%) by meclofenamate (10(-5) M), but aspirin (10(-3) M) had no such effect. Moreover, this concentration of meclofenamate reduced resting tension and inhibited by 16% the optimal responses caused by PGF2 alpha, while having no significant effect on serotonin contractions. Higher doses of meclofenamate (10(-4) M, 10(-3) M) produced increasing degrees of inhibition of contractions caused by serotonin or PGF2 alpha. Conversely, aspirin had no effect on PGF2 alpha contractions and slightly enhanced serotonin effects. The actions of indomethacin resembled those of meclofenamate. The results show clearly that different prostaglandin synthesis inhibitors have different effects on cerebral vasomotion in vitro. Aspirin, known to inhibit platelet function markedly, seems to have little effect on isolated vascular smooth muscle. On the other hand, the pharmacodynamic effects of meclofenamate and some related drugs may afford a new approach in the treatment of cerebral vasospasm.