nitroarginine and dazoxiben

To determine the role of endothelium-derived contracting factor (EDCF) in the response to endothelin-1 in arteries with regenerated endothelium.. Rings of porcine coronary arteries, with and without endothelium of previously deendothelialized left anterior descending coronary arteries and native left circumflex coronary arteries, were suspended in conventional organ chambers for the measurement of isometric force.. In quiescent rings of the previously deendothelialized left anterior descending coronary artery treated with the NO-synthase inhibitor nitro-L-arginine, endothelin-1 caused contractions which were larger in rings with than that in those without endothelium. Under the same experimental conditions, in the left circumflex coronary artery, the contractions to endothelin-1 were augmented markedly by the removal of the endothelium. In rings with endothelium of the previously deendothelialized left anterior descending coronary artery, indometacin (inhibitor of cyclooxygenase) and ridogrel (thromboxane A2 receptor antagonist and inhibitor of thromboxane synthase) inhibited contractions to endothelin-1. Dazoxiben (inhibitor of thromboxane synthase) inhibited, to the same extent as indometacin and ridogel, the response to higher concentrations of endothelin-1. The endothelium-dependent component of the response to lower concentrations of endothelin-1 was inhibited by indometacin and ridogrel, but not by dazoxiben. In rings without endothelium of both previously deendothelialized left anterior descending and native left circumflex coronary arteries, indometacin and ridogrel did not affect the contractions to endothelin-1.. These findings suggest that in regenerated endothelium, high concentrations of endothelin-1 stimulate the release of thromboxane A2. Endoperoxides generated by activation of endothelial cyclooxygenase may be the endothelium-derived contracting factor(s) released in regenerated endothelium by lower concentrations of the peptide.

Topics: Animals; Coronary Vessels; Cyclooxygenase Inhibitors; Endothelin-1; Endothelium, Vascular; Imidazoles; Indomethacin; Male; Muscle Contraction; Muscle, Smooth, Vascular; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroarginine; Pentanoic Acids; Pyridines; Swine; Thromboxane A2; Thromboxane-A Synthase

The present experiments were designed to determine the role of endothelium-derived contracting factor(s) in the contractions of the rat aorta to endothelin-1 (ET-1) and endothelin-3 (ET-3). Rings, with and without endothelium, of aortas of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were suspended in organ chambers for isometric tension recording in the presence of NG-nitro-L-arginine [NLA; inhibitor of nitric oxide synthase (NOS)]. The removal of endothelium decreased the contractions evoked by both ETs in the aorta of the SHRs but not of the WKY rats. Indomethacin (inhibitor of cyclooxygenase), dazoxiben (inhibitor of thromboxane synthase), and SQ 29,548 (antagonist of thromboxane A2 receptors) reduced the contractions to ETs in rings with, but not without, endothelium in the SHRs, whereas their effect was not endothelium dependent in the WKY rats. The presence of endothelium increased the basal and ET-stimulated release of thromboxane B2 in the aorta of the SHRs but not of WKY rats. These findings suggest that endothelium-derived thromboxane A2 contributes to contractions evoked by ET-1 and ET-3 in the aorta of the SHRs but not of the WKY rats.

Topics: Amino Acid Oxidoreductases; Animals; Aorta, Thoracic; Arginine; Bridged Bicyclo Compounds, Heterocyclic; Endothelins; Endothelium, Vascular; Fatty Acids, Unsaturated; Hydrazines; Imidazoles; In Vitro Techniques; Indomethacin; Isometric Contraction; Male; Muscle Contraction; Muscle, Smooth, Vascular; Nitric Oxide Synthase; Nitroarginine; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thromboxane A2; Thromboxane-A Synthase