Effects of isocarbacyclin, a stable prostacyclin analogue, on monkey isolated cerebral and peripheral arteries.
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.
Kawai
Y
Y
First Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
Ohhashi
T
T
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; C056566:S 145; D009599:Nitroprusside; D012701:Serotonin; C041946:9-O-methanoprostaglandin I; D011464:Epoprostenol