Effects of endothelin-1 on endothelial cells in the porcine coronary artery.
The effects of endothelin-1 (ET-1) on endothelial cells from the porcine coronary artery were investigated using cascade bioassay and radioimmunoassay methods. For comparison, endothelial cells from the rabbit abdominal aorta were also used. Freshly isolated endothelial cells were perfused with Krebs' solution. Liberation of vasodilatory substances was detected under bioassay conditions by measuring the relaxing activity of the perfusate on endothelium-denuded strips of the porcine coronary artery contracted with ET-1. The perfusate in the absence of ET-1 slightly inhibited the contraction, suggesting that endothelial cells spontaneously release vasorelaxing substances. After application of ET-1, the perfusate-induced relaxation drastically increased. Oxyhemoglobin completely abolished the relaxation induced by perfusate from endothelial cells of the rabbit abdominal aorta but only marginally attenuated the relaxation induced by perfusate from endothelial cells of the porcine coronary artery. In contrast, indomethacin significantly attenuated the relaxation induced by perfusate from the endothelial cells of the porcine coronary artery. In endothelium-intact strips of the porcine coronary artery, ET-1 significantly increased the concentration of 6-ketoprostaglandin F1 alpha but did not modify the cellular concentration of either cAMP or cGMP. It is concluded that ET-1 augments the release of vasorelaxing factors from endothelial cells both in the porcine coronary artery and in the rabbit abdominal aorta and that the major vasorelaxing substance derived from endothelial cells may be different in these two blood vessels. Prostaglandin I2 in the former and nitric oxide in the latter are suggested as possible candidates. The vasorelaxation induced by prostaglandin I2 may not be mediated by cAMP-dependent mechanisms in the porcine coronary artery.
Suzuki
S
S
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kajikuri
J
J
Suzuki
A
A
Itoh
T
T
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP