The Mechanism of hypoxic pulmonary vasoconstriction in isolated pulmonary arteries and veins

Hypoxic pulmonary vasoconstriction is an intrapulmonary adaptive mechanism in which circulating blood is diverted away from poorly ventilated to better ventilated region of the lung. It has been demostrated that precapillary arterial are the important sites of hypoxic pulmonary vasoconstriction. Additionally this vasoconstriction occurs also in large pulmonary arteries, veins and small diameter veins, this may be physilogically important. The first aim of our study is to demonstrate the effect of hypoxia in the sheep isolated pulmonary arteries and veins under resting force and when precontracted with serotonin or sodium flouride. The second aim is to determine role of G proteins in hypoxia induced vasoconstriction and clarify tyrosine kinase pathway using selective tyrosine kinase inhibitors genistein and tyrphostin and an activator phosphotidile phosphatase, sodium orto vanadat. The final aim of our experiments in sheep isolated arteries is to show the role of K+ channels in hypoxic pulmonary vasoconstriction. Although we observed a contraction in a small diameter pulmonary arteries under resting force, there was no vasoconstriction in large diameter arteries. Therefore, our results indicate that pulmonary vascular bed show regional differences to hypoxia. Genistein and tyrphostin prevented and sodium orto vanadat increased hypoxia induced vasoconstriction. These results showed that tyrosine kinase pathway mediates hypoxic pulmonary vasoconstriction. Vasoconstriction due to the lowering of pC>2 from 96 mmHg to 5 mmHg was prevented by preincubating of cholera toxin which indicates involvement of Gs proteins in the hypoxic responses. We used a K+ channels antagonist, TEA nonselective at high concentrations to examine the relationship between K+ channels and hypoxia. Our experiments demonstrated that there was no inhibition of hypoxic contractions in the presence of TEA. Therefore, these data showed hypoxia induced contraction was not dependent on K+ channels. Introduction of hypoxia induced a biphasic response with initial relaxation followed by contraction in NaF precontracted pulmonary veins. The differences in hypoxic contraction in arteries and veins suggests that different G proteins may mediates hypoxic contraction in pulmonary vascular bed. The results of our study indicate that different signal mechanisms may be activated for generation of hypoxic contraction in isolated pulmonary arteries and veins.