The importance of endogenous prostaglandins other than prostacyclin, for the modulation of contractility of some rabbit blood vessels.
Helically cut strips of rabbit aorta, extrapulmonary artery, coeliac artery, and femoral artery were set up in organ baths. Contractions of the strips by noradrenaline and angiotensin II were recorded isotonically. The release of prostaglandins 6-keto-PGF1 alpha, E2, F2 alpha, D2 and thromboxane B2 from the strips was measured by means of sensitive and specific radioimmunoassays. All blood vessels released a characteristic pattern of cyclo-oxygenase products. Prostacyclin (PGI2, measured as 6-keto-PGF1 alpha) was the major compound formed, followed by smaller amounts of PGE2 and traces of PGF2 alpha, PGD2 and thromboxane A2 (measured as thromboxane B2). The pulmonary and the femoral artery had comparatively high abilities to synthesize PGE2. Contractions induced by noradrenaline increased prostaglandin release from the pulmonary artery but not from the other blood vessels. Angiotensin II-induced contractions were accompanied by a marked prostaglandin release from the coeliac artery. After angiotensin II, prostaglandin release was also enhanced in the pulmonary artery, but remained essentially unchanged in the aorta and femoral artery. Arachidonic acid markedly increased the levels of all prostaglandin formed. Indomethacin inhibited the formation of all prostaglandins below the detection limits of the respective radioimmunoassays. Indomethacin treatment induced a qualitatively similar shifting of the concentration-response curves of noradrenaline and angiotensin II in some vessels: the concentration-response curves remained unchanged for the aorta, were slightly shifted to the left of the pulmonary artery, were markedly shifted to the left for the coeliac artery, and were shifted to the right for the femoral artery. 7 Exogenous PGI2 strongly and concentration-dependently inhibited contractions induced by the approximate EC50 of noradrenaline in the coeliac artery, but was without effect on the other three preparations. PGE2 had no effect on noradrenaline-induced contractions of the aorta, inhibited those of the pulmonary and the coeliac artery, but markedly potentiated those of the femoral artery. PGF2 alpha significantly enhanced contractions of the femoral artery, but increased contractions of the other preparations were not significant. PGD2 was without effect on any preparation. 8 In conclusion, the contractility of the aorta does not seem to be modulated substantially by prostaglandins. The major prostanoid regulating the tone of the coeliac artery was found to be PGI2. The contractility of the pulmonary and especially the femoral artery is probably not modulated by PGI2 but rather by PGE2. 9 These observations suggest that in certain blood vessels, prostaglandins other than PGI2 are important endogenous modulators of contractility.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D011458:Prostaglandins E / Q000494:pharmacology / Q000502:physiology; D011817:Rabbits
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011458:Prostaglandins E; D000804:Angiotensin II; D011464:Epoprostenol; D015232:Dinoprostone; D009638:Norepinephrine; D007213:Indomethacin