Release of endothelium-derived relaxing factors from canine cardiac valves.
In the present study, the ability of intact cardiac valvular endothelial cells to release vasodilatory prostanoids and endothelium-derived relaxing factor was investigated. Endothelium-denuded canine coronary arteries were used for bioassay and contractile force recording. Insertion of small segments of cardiac valve (20-30 mm2) with intact endothelium into endothelium-denuded coronary arterial rings did not markedly alter the sensitivity nor magnitude of the coronary artery contractile response to KCl. In contrast, the prostaglandin F2 alpha (PGF2 alpha)-induced contraction was significantly depressed (70% decrease in magnitude and 216% increase in ED50), compared with contraction in the absence of valvular endothelium (5.52 +/- 0.49 g and ED50 of 1.18 +/- 0.02 microM, respectively). These alterations in PGF2 alpha-induced contractions were reduced to 38% decrease in magnitude and +66% in ED50 in the presence of 5 microM indomethacin. Addition of acetylcholine (0.1-30 microM) into these endothelium-denuded coronary artery/valve preparations resulted in a dose-dependent relaxation, reaching a maximum of -59.9 +/- 1.6% (mean +/- SEM of seven vessels). Preincubation of valvular endothelium with 5 microM indomethacin also reduced these acetylcholine-induced valvular endothelium-dependent relaxations to 40.4 +/- 5.5% (mean +/- SEM of 13 vessels). Addition of hemoglobin (3 microM) further attenuated relaxation to -16.0 +/- 7.7% (mean +/- SEM of 14 vessels), while superoxide dismutase (20 units/ml) potentiated the relaxant response to -81.3 +/- 9.4% (mean +/- SEM of 11 vessels) in the presence of indomethacin. These findings suggest that there is a continuous basal release of vasodilatory prostanoids and endothelium-derived relaxing factor from the valvular endothelium, which can be further stimulated with acetylcholine and superoxide dismutase, and inhibited by indomethacin and hemoglobin.
Department of Pharmacology, University of Alabama, Birmingham 35294.
D D
DD
Ku
J M
JM
Nelson
J B
JB
Caulfield
M J
MJ
Winn
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006351:Heart Valves / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology
D006454:Hemoglobins; D011453:Prostaglandins; D009569:Nitric Oxide; D011189:Potassium Chloride; D015237:Dinoprost; D013482:Superoxide Dismutase; D000109:Acetylcholine; D007213:Indomethacin