Hypoxia-induced vasoconstriction in alligator (Alligator mississippiensis) intrapulmonary arteries: a role for endothelin-1?

Hypoxic pulmonary vasoconstriction (HPV) is an adaptive response that diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to better ventilated parts, matching blood perfusion to ventilation. HPV is an ancient and highly conserved response expressed in the respiratory organs of all vertebrates. However, the underlying mechanism and the role of the endothelium remain elusive. Isolated intrapulmonary arteries (internal diameter <346 microm) from the American alligator Alligator mississippiensis were mounted in microvascular myographs for isometric tension recording. Resting vessels and vessels contracted with either serotonin (5-HT) or endothelin-1 (ET-1) were exposed to sustained (45 min) hypoxia (PO2<5 mmHg). In ET-1-contracted vessels, hypoxia induced a monophasic, sustained and fully reversible constriction, which was independent of the endothelium. In relaxed or in 5-HT-contracted vessels, hypoxia did not cause constriction. The effects of ET-1, ET(A) and ET(B) as well as the general ET-receptor antagonist were studied. ET-1 caused a contraction of the pulmonary arteries through stimulation of ET(A)-receptors. ET(A) and ET(B) immunoreactive staining revealed the location of both receptors in the smooth muscle layer and of ET(B) receptors in the endothelium. In conclusion, because precontraction with serotonin did not facilitate HPV, the required precontraction in alligators seems specific to ET-1, which implies that ET-1 plays an important permissive role for the HPV response in alligators.