EFFECTS OF ISOCARBACYCLIN, A STABLE PROSTACYCLIN ANALOG, ON MONKEY ISOLATED CEREBRAL AND PERIPHERAL ARTERIES

1 The effects of isocarbacyclin (TEI 7165), a stable prostacyclin anal ogue, were examined in monkey isolated cerebral and peripheral arterie s. 2 Addition of TEI 7165 (0.1 nM-10 mu M) produced a dose-dependent r elaxation in cerebral arteries pre-contracted with 1 mu M 5-hydroxytry ptamine (5-HT). High concentrations (more than 1 mu M) Of TEI 7165 eli cited a transient contraction followed by a sustained relaxation. 3 TE I 7165 also elicited a dose-dependent relaxation in the peripheral (ex cept popliteal) arteries. The maximum relaxation induced by 10 mu M TE I 7165 was greater (P<0.05) in the mesenteric artery than in the cereb ral artery. The negative logarithm of the EC(50) value for the mesente ric, 7.6+/-0.3, was greater (P<0.05) than that for the cerebral artery , 6.4+/-0.3. The decreasing order of potency for the TEI 7165-induced relaxation was as follows: mesenteric >renal >cerebral >coronary >popl iteal. 4 Removal of the endothelium did not significantly affect TEI 7 165-induced relaxations. 5 The transient contraction produced by high concentrations of TEI 7165 was not observed in cerebral arteries preco ntracted with 1 nM U46619, a stable analogue of thromboxane A(2) (TXA( 2)). Furthermore, the TEI7165-induced contraction was markedly suppres sed(P<0.05) by treatment with 10 nM S1452, a TXA(2) blocking agent. 6 These results suggest that TEI 7165 causes an endothelium-independent relaxation in monkey cerebral and peripheral arteries, and that there is a marked regional difference in the TEI 7165-induced relaxations. A high concentration of TEI 7165 also produces a transient contraction which is probably through activation of TXA(2) (TP-) receptors.