The role of endothelial and non-endothelial prostaglandins in the relaxation of isolated blood vessels of the rabbit induced by acetylcholine and bradykinin.

Strips of rabbit extrapulmonary, coeliac and mesenteric arteries were mounted in organ baths for isotonic recording of changes in tissue length. The formation by the strips of the vasodilator prostaglandins PGI2 (measured as 6-keto-PGF1 alpha) and PGE2 was determined by specific radioimmunoassays. Removal of vascular endothelium initially increased and then permanently decreased the basal prostaglandin release of the tissues. Acetylcholine (ACh) relaxed strips of all three arteries if the endothelium was intact. ACh also stimulated the formation of PGI2 and PGE2 from all three tissues; about 60% of these prostaglandins originated from endothelial cells. Indomethacin caused complete inhibition of prostaglandins formation and a slight inhibition of the ACh-relaxation (not statistically significant). Complete inhibition of the ACh relaxation was achieved with nordihydroguaiaretic acid (NDGA). NDGA also partially inhibited prostaglandin formation. These data suggest that in blood vessels that are also prostaglandin-sensitive, the ACh relaxation is predominantly mediated by a non-prostaglandin endothelium-derived relaxing factor. Bradykinin was more potent that ACh in releasing prostaglandins from the same arteries. This release was activated in subendothelial components of the vascular wall. Neither this prostaglandin release nor the bradykinin-induced relaxations were significantly reduced in endothelium-denuded arteries. Indomethacin completely blocked the bradykinin-induced prostaglandin release and the bradykinin relaxation. NDGA caused a moderate inhibition of the bradykinin-induced prostaglandin release and slightly attenuated the bradykinin relaxation (neither effect of NDGA was statistically significant). Under all experimental conditions (control, indomethacin, NDGA) and with all three arteries there was a good correlation between the bradykinin-induced prostaglandin release and the respective mechanical response. No such correlation could be found for ACh. Prostaglandin-dependent relaxations of the coeliac and mesenteric artery are probably mediated by endogenous PGI2. The extrapulmonary artery is rather insensitive to PGI2 and is probably relaxed mainly by endogenous PGE2.