EFFECTS OF HYPOXIA ON PULMONARY VASCULAR CONTRACTILITY

Although hypoxic pulmonary vasoconstriction (HPV) has been recognized by many researchers, the precise mechanism remains unknown. As isolate d pulmonary arteries will constrict in vitro in response to hypoxia, t he oxygen sensor/transduction mechanism must reside in the pulmonary a rterial smooth muscle or in the endothelium, or in both. Unfortunately , much of the current evidence is conflicting, especially as to the de pendency of HPV on the endothelium and the role of a K+ channel. There fore, this experiment was attempted to clarify the dependency of HPV o n the endothelium and the role of a K+ channel on HPV in rat pulmonary artery. The effects of hypoxia were investigated in isolated main pul monary arteries precontracted with norepinephrine. Vascular rings were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit solution. Hypoxia was induced by gassing the ch amber with 95% N-2 + 5% CO2 and this was maintained for 20 min. Hypoxi a elicited a vasoconstriction in arteries with endothelium. Mechanical disruption of the endothelium abolished HPV. There was no difference between the amplitude of the HPV induced by two consecutive hypoxic ch allenges and the effect of normoxic and hyperoxic control Krebs-Hensel eit solution on a subsequent response to hypoxia. Inhibition of NO syn thesis by treatment with N-omega-nitro-L-arginine reduced HPV, but inh ibition of a cyclooxygenase pathway by treatment with indomethacin had no effect on HPV. Blockades of a tetraetylammonium chloride-sensitive K+ channel abolished HPV. Verapamil, a Ca2+ entry blocker reduced HPV . In conclusion, these results suggest that HPV was dependent on the e ndothelium and that HPV can be considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation such as the opening of a K+ channels.