ENDOTHELIAL MODULATION OF PH-DEPENDENT PRESSOR-RESPONSE IN ISOLATED-PERFUSED RABBIT LUNGS

With the use of isolated perfused rabbit lungs (n = 152), roles of end othelium-derived relaxing factor (EDRF) in pulmonary vascular response s to hypocapnia and hypercapnia were studied. Lungs were ventilated wi th a gas mixture containing 1, 5, or 10% CO2 and 21% O-2, adjusting th e perfusate pH to 7.8, 7.4, or 7.1, respectively. Methemoglobin (MetHb ), hemoglobin (Hb), methylene blue (MB), and L-argininosuccinic acid ( L-ASA) were used as modulators of EDRF. To eliminate augmented shear s tress, we used papaverine during hypercapnia. As a measure of EDRF, we spectrophotometrically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnia and hypercapnia evoked, respectively, unsustaina ble vasodilatation and vasoconstriction. Hb, MB, and L-ASA, but not Me tHb, produced an increase in baseline pulmonary arterial pressure (P-p a), These agents also exacerbated vasoconstriction during hypercapnia. Hypercapnia and hypocapnia caused an increase and decrease, respectiv ely, in EDRF production. L-ASA suppressed EDRF production in hypercapn ic lungs. Papaverine did not suppress EDRF production under hypercapni a. In conclusion, 1) the effects of pH on pulmonary circulation are tr ansient, 2) the increase in P-pa caused by hypercapnia is modulated by EDRF, and 3) the pulmonary EDRF genesis is activated by hypercapnic a cidosis but suppressed by hypocapnic alkalosis.