Effects of isocarbacyclin, a stable prostacyclin analogue, on monkey isolated cerebral and peripheral arteries.

Abstract

1. The effects of isocarbacyclin (TEI 7165), a stable prostacyclin analogue, were examined in monkey isolated cerebral and peripheral arteries. 2. Addition of TEI 7165 (0.1 nM-10 microM) produced a dose-dependent relaxation in cerebral arteries pre-contracted with 1 microM 5-hydroxytryptamine (5-HT). High concentrations (more than 1 microM) of TEI 7165 elicited a transient contraction followed by a sustained relaxation. 3. TEI 7165 also elicited a dose-dependent relaxation in the peripheral (except popliteal) arteries. The maximum relaxation induced by 10 microM TEI 7165 was greater (P < 0.05) in the mesenteric artery than in the cerebral artery. The negative logarithm of the EC50 value for the mesenteric, 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 > popliteal. 4. Removal of the endothelium did not significantly affect TEI 7165-induced relaxations. 5. The transient contraction produced by high concentrations of TEI 7165 was not observed in cerebral arteries precontracted with 1 nM U46619, a stable analogue of thromboxane A2 (TXA2). Furthermore, the TEI 7165-induced contraction was markedly suppressed (P < 0.05) by treatment with 10 nM S1452, a TXA2 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 TXA2 (TP-) receptors.