CONTINUOUS BASAL FORMATION OF ENDOTHELIUM-DERIVED RELAXING FACTOR AND MUSCLE-DERIVED RELAXING FACTOR, BOTH OF WHICH ARE NITRIC-OXIDE

The objective of this study was to ascertain the role of both the vascular endothelium and smooth muscle in the continuous regulation of pulmonary vascular smooth muscle tone. Isolated rings of endothelium-intact and endothelium-denuded bovine pulmonary artery and vein were studied. Competitive inhibitors of nitric oxide (NO) synthase activity (N(G)-amino-L-arginine and N(G)-nitro-L-arginine) or NO action (hemoglobin) contracted arterial and venous rings in the presence or absence of endothelium, and contractile responses were accompanied by marked decreases in endogenous guanosine-3',5'-cyclic monophosphate (cyclic GMP) levels. L-Arginine failed to relax freshly isolated arterial rings but caused endothelium-independent relaxation of, and elevation of cyclic GMP levels in, rings that had been incubated for 16-24 h to deplete rings of endogenous L-arginine. Incubation of endothelium-denuded arterial rings with lipopolysaccharide or interleukin-1 for 16 h caused a marked cycloheximide-sensitive tissue accumulation of cyclic GMP and nitrite (NO2-). These studies indicate that both the pulmonary vascular endothelium and smooth muscle continually release NO in quantities sufficient to maintain a decreased vascular smooth muscle tone.