15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and nictindole

Isolated coronary arteries from diabetic dogs presented different contractile response to U-46619 to prostacyclin (PGI2) and to arachidonic acid (AA) than those of normal dogs. The stimulatory effect of the synthetic endoperoxide analogue U-46619, was significantly higher in the diabetic condition than in preparations from normal animals. On the other hand, while PGI2 evoked a dose-dependent relaxation of normal coronary arteries, diabetic vessels were not relaxed by low concentration of PGI2 whereas higher ones produced a distinct constrictor effect. Additionally, inhibitors of prostaglandins and thromboxane (TX) biosynthesis such as corticosterone, indomethacin, acetylsalicylic acid, imidazole and L-8027, abolished the stimulatory effect of PGI2 in coronary arteries from diabetic dogs. AA relaxed coronaries from normal dogs and constricted those from diabetic animals, this action being inhibited by imidazole and L-8027. The present results suggest that: a) coronary vessels from diabetic dogs are more reactive to an endoperoxide analogue than normal preparations and b) PGI2 and AA probably contract diabetic coronary arteries via the participation of a TX like material. It is then plausible that this effect could be tentatively ascribed to the production of a prostaglandin constricting substance including also the probable generation of a TXA2-like agonist.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Anti-Inflammatory Agents; Aspirin; Coronary Vessels; Corticosterone; Diabetes Mellitus, Experimental; Dogs; Dose-Response Relationship, Drug; Epoprostenol; Imidazoles; Indoles; Indomethacin; Kinetics; Pancreatectomy; Prostaglandin Endoperoxides, Synthetic; Prostaglandins; Pyridines