Cerebrovascular effects of prostanoids. In-situ studies in pial arteries of the cat

Abstract

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 feline and rat pial arteries in-situ using perivascular microapplication and measurement of vascular diameter. U46619 induced a concentration-dependent vasoconstriction with a maximal response of 24% at 10(-6) mol.l-1 and an EC50 of 4.9 x 10(-8) mol.L-1. This effect was inhibited by the thromboxane receptor blocking drugs AH23848 B [[1 alpha(z),2 beta,5 alpha]-(+/-)-7-[5-[(1,1'-(biphenyl)-4- yl]methoxy]-2-(4-morpholinyl)-3-oxocyclo-pentyl]-4-heptenoic acid)] and EP092 [(+/-)-5-endo-(6'-carboxyhex-2'z-enyl)-6-exo[1'-[N- (phenylthiocarbamoyl)-hydrazano]-ethyl]-bicyclo[2,2,1]-hepta ne], indicating the involvement of thromboxane-prostanoid-receptors. PGF2 alpha produced vasodilatation in cats with an increase in vessel diameter of 30% at 10(-3) mol.l-1, but constricted rat pial arteries concentration-dependently with a maximal response of 23% at 10(-4) mol.l-1. PGE2 and iloprost induced concentration-dependent (10(-9)-10(-5) mol.l-1)) dilatations with apparent maximal responses of 39% and 34% at 10(-5) mol.l-1, respectively. The corresponding EC50 values were 2.45 x 10(-7) mol.l-1 (PGE2) and 3.5 x 10(-7) mol.l-1 (iloprost). These data demonstrate the presence of prostanoid receptors mediating constriction and dilatation under in-situ conditions.(ABSTRACT TRUNCATED AT 250 WORDS)