POTASSIUM CHANNELS ARE NOT INVOLVED IN VASOPRESSIN-INDUCED VASODILATION IN THE RAT LUNG

We have previously observed that arginine vasopressin (AVP)-induced pu lmonary vasodilation is attenuated by nitric oxide (NO) synthesis inhi bition; however, blockade of the response is incomplete even at very h igh doses of the inhibitor. Thus it was hypothesized that the remainin g vasodilation might be due to release of an endothelium-derived hyper polarizing factor acting to open vascular smooth muscle K+ channels. L ungs were isolated from male Sprague-Dawley rats and perfused at const ant flow with physiological saline solution containing 4% albumin. Aft er equilibration, lungs were treated with either glibenclamide (50 mu M), Ba2+ (100 mu M), tetraethylammonium (10 mM), or the respective veh icle and were then constricted with the thromboxane mimetic U-46619. U pon development of a stable degree of vasoconstriction, AVP (2.5 x 10( -9) M) was administered and its vasodilator action noted. AVP caused a n similar to 60% reversal of U-46619 vasoconstriction in control lungs , and this response was not affected by any of the K+ channel blockers . In contrast, administration of the NO synthesis inhibitor N-omega-ni tro-L-arginine (L-NNA; 300 mu M) significantly attenuated AVP-induced dilation to similar to 25%. The addition of K+ channel blockers did no t further diminish the vasodilatory response in L-NNA-treated lungs. I n conclusion, these results suggest that ATP- and Ca2+-sensitive K+ ch annels are not involved in the pulmonary vasodilatory response to AVP.