Cerebrovascular effects of prostanoids: In Vitro studies in feline middle cerebral and basilar artery

Abstract

The efect of prostaglandin (PG) E 2, F 2α, the thromboxane-A 2 mimetic U46619 (9,11-dideoxy-9α, 11α-methaneopoxy-prostaglandin F 2α) and the prostacyclin mimetic iloprost was investigated in cat middle cerebral and basilar arteries in vitro precontracted with 5-hydroxytryptamine (5-HT) (50nM) in the absence and presence of the cyclooxygenase inhibitor indomethacin or the thromboxane receptor blocker AH23848b [1α(z), 2β, 5α]-(+)-7-[5-[1,1′-(biphenyl)-4-yl] methoxy]-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid). PGF 2α and U46619 both produced further concentration-related contractions of basilar and middle cerebral artery, U46619 being approximately 1,000 times more potent than PGF 2α. Iloprost produced concentration-related relaxations of precontracted basilar and middle cerebral artery, the mean maximum relaxations produced at a concentration of 1.3μM being 57.3% and 80.6%, respectively of the contraction produced by 50nM 5-HT. PGE 2, 100nM relaxed the basilar and middle cerebral artery, 46.7% and 38.5% respectively. However, at 1μM, PGE 2 caused contraction. Indomethacin, 2.8μM had no effect on contractile or relaxant responses to any of the prastanoids. Oxyhaemoglobin inhibited the relaxation of both arterial preparations but had no effect on responses to PGE 2 or iloprost. The thromboxane-receptor blocker AH23848B antagonised the contractile responses to U46619, PGF 2α and PGE 2 and had no effect against relaxant responses to PGE 2 or iloprost. It is concluded that both contraction- and relaxation-inducing prostanoid receptors are present in the in vitro preparation of feline basilar and middle cerebral artery. Under sustained tension conditions, endothelial factors do not appear to be involved in the responses to dilating prostanoids.