DIFFERENT RESPONSES OF ARTERIOLES AND VENULES IN RAT GASTRIC-MUCOSAL MICROCIRCULATION TO ENDOTHELIN-1 AND ENDOTHELIN-3

Responses of the microvessels in the basal part of the gastric mucosa of anesthetized rats to endothelin (ET)-1 and ET-3 were examined by in travital microscopy. The posterior wall of the stomach, which was inci sed along the greater curvature, was secured in an observation chamber and superfused with Tyrode's solution, and the microcirculation was o bserved through a window made by removing a limited area of smooth-mus cle layers with the serosa and submucosal tissue. Topical application of the same ranges of ET-1 and ET-3 (0.1-10 mu M, 20 mu l) to the wind ow dose-dependently constricted collecting venules and venules downstr eam. The constriction was inhibited by BQ-123, an ET(A) receptor antag onist, but the equipotency of ET-1 and ET-3 did not support the presen ce of the ET(A) receptor (tentatively called ETR-m). Arterioles were c onstricted through ETR-m, particularly at higher doses (> 3 mu M), but 1 mu M ET-1 dilated the arterioles by generating prostaglandin throug h BQ-123-sensitive ET receptor (tentatively called ETR-e), as shown by the inhibition of dilatation by indomethacin. Furthermore, the dilata tion component of the arteriolar smooth-muscle responses to ET-1 and E T-3 was elicited by BQ-123 and was inhibited by N-G-monomethyl-L-argin ine (L-NMMA), indicating the generation of nitric oxide. This dilating effect of the endothelins was mediated by the ET(B) receptor.