Segmental pulmonary vascular responses to changes in pH in rat lungs: roleof nitric oxide

Background: Respiratory or renal failure is associated with changes in bloo d pH. Changes in pH may have profound effects on vascular tone and reactivi ty. Site of action of acidosis in the pulmonary vasculature and the role of nitric oxide production remain unclear. Methods: We utilized isolated rat lung preparation perfused with autologous blood (Hct = 20%, flow rate = 33 ml/min), and investigated the effect of a cidosis and alkalosis (induced by ventilation with high and low inspired CO 2) on vascular resistance and the role of nitric oxide during resting and e levated tone conditions. Changes in resistance were described in terms of s mall and large arteries and veins, using the vascular occlusion technique. Results: Acidosis (P-CO2 = 66.7 +/- 0.7 mmHg, pH = 7.17 +/- 0.01, P-O2 = 25 5 +/- 3 mmHg) caused vasoconstriction under resting and increased vascular tone conditions (U46619-induced). The changes in resistance occurred primar ily in the small arteries. In contrast, alkalosis (P-CO2 = 20.1 +/- 0.3 mmH g, pH = 7.61 +/- 0.01, P-O2 = 244 +/- 3 mmHg) caused vasodilation only at e levated tone conditions. Nitrow-L-arginine (LNA), an inhibitor of nitric ox ide synthase, increased vascular resistance slightly but did not modulate t he responses to pH, suggesting that such responses are not nitric oxide dep endent. During KCl-induced contraction, the effects of pH were abolished. Conclusions: We conclude that in rat lung, acidosis causes an increase in p ulmonary vascular resistance at normal and elevated tone conditions. Furthe rmore, the response is limited primarily to the small arteries, and is not mediated by nitric oxide. Alkalosis tends to cause the opposite effects. Th e effects of acidosis and alkalosis were abolished when vascular tone was e levated with a low dose of KCl, suggesting that vascular response to pH may involve changes in membrane potential.