肺循環とプロスタノイド 特に低酸素性肺血管収縮におけるプロスタノイドの関与

Abstract

Hypoxic pulmonary vasoconstriction (HPV) is known to be an important physiological response to preserve an appropriate ventilation-perfusion ratio in the lung. The precise mechanism of HPV remains to be controversial, but recently the role of prostaglandins for mediating and/or modulating HPV has been emphasized. From this viewpoint, we studied the effect of PAF on HPV in anesthetized, open chest mongrel dogs. HPV was assessed by the change of total pulmonary resistance (TPR, PPA-PLA/QAO) . After the stable condition was established, 15-min exposure to 10% O2 followed by 15-min exposure to 100% O2 was repeated 6 times.In control group (N=5), spontaneous potentiation of HPV was observed during the 1st to the 5th hypoxic exposures, but an attenuation was occurred in the 6th hypoxic exposure.In PAF treatment group (N=5), the 6th hypoxic exposure was performed during continuous infusion of PAF at the dose of 33 ng/kg/min for 30 min (totally 1μg/kg) . This group showed no attenuation but potentiation of HPV in the 6th hypoxic exposure.Pretreatment with CV-3988 (10mg/kg), a specific antagonist of PAF, blocked the potentiating effect on HPV induced by PAF but pretreatment with OKY-046 (10mg/kg), a specific thromboxane synthetase inhibitor, did not block the effect of PAF.It is suggested that PAF, at the dose of 1μg/kg, acts as vasoconstrictor even in the condition of elevated pulmonary vascular tone induced by HPV in mongrel dogs.