Endothelin (ET) receptor interaction does not occur in vena cava from ET B receptor deficient rats

We previously observed functional ET A and ET B receptor cross‐talk in rat vena cava. We hypothesized that ET A and ET B receptor interaction would not occur in vena cava from ET B receptor deficient rats (sl/sl) compared to their wild‐type counterparts (+/+). We compared isometric contraction to ET‐1 during ET A receptor blockade, ET B receptor blockade and ET A +ET B receptor blockade in rings of thoracic aorta and vena cava from +/+ and sl/sl rats. Vena cava from sl/sl rats did not contract to the ET B receptor agonist sarafotoxin 6c (S6c, 100 nM), while vena cava from +/+ rats contracted to S6c [73±10 % norepinephrine (10 μM) contraction]. In vena cava from sl/sl rats, ET B receptor blockade did not alter ET A receptor sensitivity to receptor blockade, while in vena cava from +/+ rats, ET B receptor blockade increased ET A receptor sensitivity to receptor blockade (Table 1). Our data demonstrate that vena cava from sl/sl rats express dysfunctional ET B receptors that do not functionally interact with ET A receptors, similar to aortic ET B receptors. These results suggest that a contractile ET B receptor is key to functional ET A and ET B receptor interaction. 1 Estimated pD 2 values (−log M) for ET‐1‐induced contraction in vena cava from +/+ and sl/sl rats