ETB receptors contribute to venous but not arterial constriction caused by ET‐1: studies using ETB receptor‐deficient rats

ET‐1 is more potent in contracting veins than arteries. We hypothesized that ET‐1 contracts veins, but not arteries, by acting at ET A (ET A R) and ET B receptors (ET B R). Using ET B R deficient (−/−), +/+ and +/− rats, we studied ET‐1 constrictions of mesenteric arteries and veins (150–300 μm) in vitro . Veins were more sensitive than arteries to ET‐1 in +/− and +/+ rats, but not in −/− rats. The ET B R agonist, S6c, constricted veins, but not arteries, from +/+ and +/− rats. S6c did not constrict −/− veins. An ET A R antagonist, (ABT627), but not BQ‐788 (ET B R antagonist) blocked arterial ET‐1 responses. ABT627 reduced ET‐1 responses in +/+ and +/− veins and blocked responses in −/− veins. BQ‐788 did not affect ET‐1 responses in any vein. Antagonist co‐application blocked ET‐1 responses in +/+ and +/− veins suggesting an ET A R and ET B R interaction. ET‐1 responses desensitized in all arteries and in −/− veins. Veins from +/+ and +/− rats were resistant to desensitization. Immunocytochemistry revealed that ET A R localized to the membrane of arterial and venous smooth muscle cells (VSMCs), while ET B Rs were intracellular in arteries. ET B Rs localized to the membrane of +/+ and +/− VSMCs. In −/− VSMCs, ET A Rs, but not ET B Rs, were in the membrane. We conclude that membrane expression of ET B R in VSMCs accounts for: increased sensitivity of veins to ET‐1 compared to arteries; venous resistance to ET‐1 desensitization.