Significance of Endothelium-Derived Relaxing Factor (EDRF) on Pulmonary Vasoconstriction Induced by Hypoxia and Hypercapnia

Abstract

Distribution of pulmonary blood flow is physiologically regulated by alveolar PO₂ and PCO₂ surrounding the microcirculation in the lung (Fishman, 1976; Yamaguchi et al., 1994). Decrease in PO₂ and/or increase in PC0₂ has been considered to evoke a rise in the pulmonary microvascular resistance to blood flow (Sylvester et al., 1986; Rodman and Voelkel, 1991). It has been suggested that hypoxic pulmonary vasoconstriction (HPV) as well as hypercapnic-induced vasoconstriction may divert blood flow away from the poorly ventilated areas (Fishman, 1976). The importance of the endothelial-derived vasoactive agents in modulating blood flow has been increasingly recognized since the discovery of endothelium-derived relaxing factor (EDRF), a noble vasodilator of both the systemic and pulmonary circulation (Palmer et al., 1987; Ignaro et al., 1987; Moncada et al., 1991). Many authors have attempted to clarify a possible role of EDRF in the occurrence of HPV, however definite conclusion has not been attained. Although hypercapnia caused by alveolar hypoventilation is considered as the additionally important factor affecting pulmonary hemodynamics (O’Brodovich et al., 1982; Marshall et al., 1984; Sylvester et al., 1986; Yamaguchi et al., 1994), there have been no systematic studies showing the potential effects of hypercapnic-induced acidosis on EDRF modulation for pulmonary circulation. The first aim of this study is systematically to reinvestigate the effects of EDRF on HPV applying varied inhibitors or inactivators for EDRF acting on different levels of EDRF metabolic pathway. The second aim is to make clear the possible roles of EDRF modulating the pulmonary vascular response to acute hypercapnia.