Effects of prostaglandin I2 synthesized in the endothelium and in the smooth muscle on mechanical properties of the canine thoracic aorta.
In circular-cut strips prepared from canine thoracic aorta, acetylcholine (ACh) and A23187 relaxed endothelium-intact tissues [E(+) preparations] pre-contracted with noradrenaline or excess concentrations of K. These relaxations were associated with marked increases in the amount of 6-keto PGF1 alpha. After removal of the endothelium [E(-) preparations] the relaxation ceased, and the amounts of 6-keto PGF1 alpha were markedly reduced. In E(+) preparations, application of indomethacin attenuated the increase in 6-keto PGF1 alpha induced by ACh or A23187 in the presence of noradrenaline or high K, but not the endothelium-dependent relaxations. In E(-) preparations, ACh (0.1-10 microM) neither increased the amount of 6-keto PGF1 alpha nor produced a contraction. In dispersed single endothelial cells, A23187 markedly increased but 118 mM K did not modify the amount of 6-keto PGF1 alpha. Both noradrenaline and high K increased the production of 6-keto PGF1 alpha in the E(-) preparations but to a lesser extent than that in the E(+) preparations. This action was attenuated by indomethacin. The amplitude of the noradrenaline- and K-induced contractions was enhanced with indomethacin pretreatment in both E(+) and E(-) tissues. PGI2-Na (10 nM), reduced the amplitude of noradrenaline-induced contractions, concentration dependently and to the same extent in both E(+) and E(-) preparations. These results indicate that synthesis of PGI2 in the endothelium is not causally related to the endothelium dependent relaxation. PGI2 synthesized in the endothelium may not act directly on the muscle tissue, but PGI2 synthesized in the smooth muscle tissue may produce an inhibition of contraction.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D004285:Dogs; D004727:Endothelium / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis / 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 / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology
D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin