ENDOTHELIUM-DEPENDENT CONTRACTIONS TO ENDOTHELIN IN THE RAT AORTA ARE MEDIATED BY THROMBOXANE-A(2)

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 N(G)-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.