Role of endothelium derived nitric oxide (EDNO) and hyperpolarizing factor (EDHF) in different segments of the pulmonary vasculature in rabbit lung

EDHF and EDNO are thought to play different roles in small and large vessels. We used isolated rabbit lungs perfused with blood (Flow = 200 ml/min, Hct=20%) and pretreated with indomethacin. We studied the effect of nitro-L-arginine (LNA, 0.2 mg/ml), inhibitor of NO synthesis, tetraethylammonium (TEA, 10 mM) , inhibitor of potassium channels, and KCl (25 mM), a depolarizing agent to inhibit the effect of EDHF, on pulmonary vascular resistance (PVR). The modified vascular occlusion analysis (Eur Reap J 9:1996) was used to partition PVR into large arteries (Ra), small arteries (Rsa), small veins (Rsv) and large veins (Rv). LNA had no effect on PVR during basal conditions. In contrast, KCl caused a significant increase in PVR due to an increase in Ra and Rsa. The effects of TEA (not shown) were similar to those of KCl. When KCl was high (25 mM), LNA caused a marked rise in Ra and Rsa. The results suggest that EDHF is the primary regulator of vascular tone, while EDNO plays a secondary role in rabbit lung.