Role of NO and Prostaglandins in Acute Hypoxic Vasoconstriction in Sheep Pulmonary Veins

Abstract

The aim of this study was to investigate the effect of hypoxia on and the role of nitric oxide (NO) and cyclooxgenase inhibition in hypoxia-induced vasoconstriction in sheep isolated pulmonary veins. We used the potent pulmonary vasoconstrictor U46619, a thromboxane analog, as a precontractile agent. Our results showed that hypoxia caused a vasoconstriction both under resting tone and in U46619 (10^–6 mol/l) precontracted pulmonary veins. In the presence of the nonselective NO synthase inhibitior Nω-nitro-L-arginine methyl ester (L-NAME; 3 × 10^–5 mol/l), the hypoxic pulmonary vasoconstriction (HPV) was significantly increased in veins under resting force. However, there was a decrease in HPV in pulmonary veins precontracted with U46619 in the presence of L-NAME. Moreover, L-NAME markedly augmented the U46619-induced pulmonary contractions under normoxic conditions. Cyclooxygenase inhibition with indomethacin (10^–5 mol/l) significantly reduced the HPV both under resting tone and in precontracted veins. Indomethacin also significantly decreased the U46619-induced pulmonary contractions prior to the induction of hypoxia. Our findings suggest that NO and prostaglandins can act as a modulators of the hypoxic vasoconstriction in isolated pulmonary veins.

Role of ATP-sensitive potassium channels on hypoxic pulmonary vasoconstriction in endotoxemia

“…Inhibition of NOS by L-NAME augments HPV dose-dependent in blood perfused isolated rat lungs, whereas it has no effect on buffer perfused rat lungs [ 44 , 45 ]. There was no change by L-NAME in baseline perfusion pressure in buffer perfused isolated perfused rabbit or mouse lungs [ 46 , 47 ].…”

Inhibition of ornithine decarboxylase restores hypoxic pulmonary vasoconstriction in endotoxemic mice

“…Indomethacin was shown to increase HPV in a canine model of oleic acid-induced acute lung injury but decreased HPV in sheep pulmonary veins and had no effect in a murine model of HPV. [22][23][24] By adding the nonselective NOS inhibitor L-NAME to the perfusion buffer, acute NO-dependent effects on HPV were excluded. Excessive NO production during septic shock causes systemic hypotension.…”

“…The role of cyclooxygenase inhibitors in modulating HPV is not clear. Indomethacin was shown to increase HPV in a canine model of oleic acid‐induced acute lung injury but decreased HPV in sheep pulmonary veins and had no effect in a murine model of HPV 22–24 . By adding the nonselective NOS inhibitor L‐NAME to the perfusion buffer, acute NO‐dependent effects on HPV were excluded.…”