Endothelium-derived relaxing factor is a selective relaxant of vascular smooth muscle.
The present study examines the relaxant selectivity of endothelium-derived relaxing factor (EDRF) released from cultured endothelial cells. Endothelial cells from bovine pulmonary artery (CCL-209) in culture were grown on Cytodex-3 microcarrier beads, packed into a column and superfused to release EDRF. EDRF response was estimated by its ability to relax phenylephrine-contracted rings of rabbit aorta. Bradykinin and A23187 (10(-10) to 10(-6) M) caused dose-dependent release of EDRF from cultured bovine pulmonary artery endothelial cells. The release was dependent on endothelial cell number. A23187 caused a larger and longer-lasting release of EDRF than bradykinin. EDRF relaxation was selective for blood vessels. EDRF relaxed rabbit aortic rings, but it did not relax histamine-contracted guinea pig tracheal, rabbit taenia coli strips or oxytocin-contracted guinea pig uterine rings. These nonvascular smooth muscles were, however, relaxed by isoproterenol (10(-4) M) and sodium nitroprusside (SNP, 10(-5) M). The sensitivity of guinea pig aortic rings and tracheal strips to SNP were compared. The IC50 values for SNP (10(-9) to 10(-5) M) were 0.07 and 0.3 microM for aortic rings and tracheal strips, respectively. Although the tracheal strips were about 4-fold less sensitive than the aorta toward SNP, a complete relaxation was achieved. These results suggest that EDRF relaxes vascular smooth muscles but not respiratory, Gl or reproductive smooth muscles. Thus, EDRF may be a selective relaxant of vascular smooth muscle.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001688:Biological Products / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide; D011651:Pulmonary Artery; D011817:Rabbits; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D001688:Biological Products; D009569:Nitric Oxide; D007213:Indomethacin