Cerebrovascular effects of prostanoids: in-vitro studies in feline middle cerebral and basilar artery.
The effect of prostaglandin (PG) E2, F2 alpha, the thromboxane-A2 mimetic U46619 (9,11-dideoxy-9 alpha,11 alpha-methanoepoxy-prostaglandin F2 alpha) 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 [1 alpha (z),2 beta,5 alpha]-(+)-7-[5-[1,1'-(biphenyl)-4-yl] methoxy]-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid). PGF2 alpha and U46619 both produced further concentration-related contractions of basilar and middle cerebral artery, U46619 being approximately 1,000 times more potent than PGF2 alpha. Iloprost produced concentration-related relaxations of precontracted basilar and middle cerebral artery, the mean maximum relaxations produced at a concentration of 1.3 microM being 57.3% and 80.6%, respectively of the contraction produced by 50nM 5-HT. PGE2, 100nM relaxed the basilar and middle cerebral artery, 46.7% and 38.5% respectively. However, at 1 microM, PGE2 caused contraction. Indomethacin, 2.8 microM had no effect on contractile or relaxant responses to any of the prostanoids. Oxyhaemoglobin inhibited the relaxation of both arterial preparations but had no effect on responses to PGE2 or iloprost. The thromboxane-receptor blocker AH23848B antagonised the contractile responses to U46619, PGF2 alpha and PGE2 and had no effect against relaxant responses to PGE2 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.
Whalley
E T
ET
Dept. of Physiological Sciences, University of Manchester, U.K.
Schilling
L
L
Wahl
M
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D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D016285:Iloprost; D008297:Male; D009119:Muscle Contraction; D009126:Muscle Relaxation; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*
D002317:Cardiovascular Agents; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D015237:Dinoprost; D011464:Epoprostenol; D016285:Iloprost; D015232:Dinoprostone