急性 Hypoxia 時の肺血管攣縮にあづかるレニンーアンジオテンシン系とプロスタグランデンの相互作用に関して

抄録

The present investigation was undertaken to clarify the role of the interaction of the renin-angiotensin system with prostaglandins (PGs) in the mediation of the pulmonary pressor response to alveolar hypoxia. In isolated rat lungs perfused with a Krebs-bicarbonate buffer containing 4.5% of bovine serum albumin, the addition of angiotensin I (A I, 12ng/ml) or angiotensin II (A II, 10ng/ml) to the perfusate augmented the pulmonary pressor response to hypoxia (100% N₂) markedly in doses that were themselves subpressor, while the addition of neither bradykinin (20ng/ml) nor noradrenalin (20ng/ml) elicited the same effects. Simultaneous infusion of bradykinin potentiator C, a potent inhibitor of A I converting enzyme, with A I abolished the potentiation of hypoxic pulmonary pressor response by A I, but no such effect was observed with A II. Addition of aspirin (300μg/ml), a potent inhibitor of PGs biosynthesis, to the perfusate enhanced further the hypoxic pressor response augmented by A II. The pulmonary pressor response to A II was also potentiated by aspirin, while that to PG F_2α was not influenced. Effects of PG E₁ and PG E₂ on hypoxic pulmonary pressor response were also investigated. PG E₁ (40ng/ml) reduced hypoxic pressor response and, in contrast, PG E₂ augmented it.
Based on these results, it could be concluded that the enhanced pulmonary hypoxic pressor response by aspirin might be due to the prevention of a secondary release of vasodilating PG E₁ during pulmonary vasoconstriction induced by alveolar hypoxia. PG E₂ might be released specifically under the influence of A II. An action of PG E₂ could also be required for a significant vasoconstrictive response to hypoxia in isolated rat lungs. Although it remains to be seen whether the interaction of renin-angiotensin system with prostaglandins do more than contribute to the initial tone, studies of the effects of the interaction of these vasoactive substances on pulmonary vascular resistance during alveolar hypoxia could lead to a better understanding of the pathogenesis of hypoxic pulmonary hypertension in vivo.