Endogenous endothelins and nitric oxide in hypoxic pulmonary vasoconstriction

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Abstract
The effects of endothelin receptor blockade on the pulmonary circulation have been reported variably, possibly in relation to a more or less important associated release of endogenous nitric oxide (NO). The aim of this study was to test whether endothelin antagonism would inhibit hypoxic pulmonary vasoconstriction, and if it would not, then would it do so after NO synthase inhibition.Hypoxic pulmonary vasoconstriction (HPV) was evaluated in anesthetised dogs by the increase in the mean pulmonary artery pressure (Ppa) minus occludedPpa(Ppao) gradient in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow.Bosentan, an endothelin A and B receptor antagonist, did not affect baselinePpa,Ppaoor systemic arterial pressure (Psa) and did not alter HPV (n=8). The NO synthase inhibitor NG­nitro‐l‐arginine (l‐NA) did not affect baselinePpaandPpao, but increasedPsaand enhanced HPV (n=12). The addition of bosentan in these dogs did not affect baselinePpaorPpao, but decreasedPsaand inhibited HPV. Exhaled NO was decreased byl‐NA and by bosentan and abolished byl‐NA+bosentan (n=9).The authors conclude that endogenous nitric oxide is released by, and opposes the vasoconstricting effects of, endothelinsin vivo, reducing systemic blood pressure and limiting hypoxic pulmonary vasoconstriction.