Endothelial modulation on ph-dependent pressor response in isolated perfused rabbit lungs. Yamaguchi, Kazuhiro, Tomoaki Takasugi, Hirohumi Fujita, Masaaki Mori, Yoshitaka Oyamada, Kohichi Suzuki, Atsushi Miyata, Takuya Aoki, and Yukio Suzuki. Department of Medicine, School of Medicine, Keio University, Tokyo 160, Japan
APStracts 2:0317H, 1995.
Using isolated perfused rabbit lungs (n=152), we attempted to clarify the roles of endothelium-derived relaxing factor (EDRF) in pulmonary vascular responses to hypocapnic alkalosis and to hypercapnic acidosis. The perfusate was a modified Krebs-Henseleit solution without blood. Isolated lungs were ventilated with a gas mixture containing 1, 5 or 10% CO2 while maintaining the O2 concentration at 21%, adjusting the 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 stress, we used papaverine during hypercapnic ventilation. As a measure of EDRF, we spectrophotometorically examined nitric oxide (NO) metabolites in the perfusate. Hypocapnic alkalosis and hypercapnic acidosis evoked, respectively, unsustainable vasodilation and vasoconstriction. Hb, MB and L-ASA, but not MetHb, produced an increase in baseline pulmonary arterial pressure (Ppa) in both the alkalosis and the acidosis protocol. These agents also exacerbated vasoconstriction under conditions of hypercapnic acidosis. Hypercapnic acidosis and hypocapnic alkalosis caused an increase and decrease, respectively, in EDRF production. L-ASA suppressed EDRF production in hypercapnic lungs. Papaverine did not suppress EDRF production under hypercapnic conditions. In conclusion, 1) the effects of pH on pulmonary circulation are transient. 2) the increase in Ppa caused by hypercapnic acidosis is clearly modulated by EDRF. 3) pulmonary EDRF genesis appears to be activated by hypercapnic acidosis but suppressed by hypocapnic alkalosis. 

Received 23 February 1995; accepted in final form 13 July 1995.
APS Manuscript Number H1073-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.