|Budget Amount *help
¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1996 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1995 : ¥600,000 (Direct Cost : ¥600,000)
This study was conducted to investigate the role of endogenous nitric oxide (NO) in regulating pulmonary vascular tone under basal and hypertensive conditions. To this end, we directly measured internal diameter responses to NO synthesis inhibition in small muscular pulmonary arteries and veins (100-1000 mum ID), using an X-ray television system on the in vivo cat or rat lung.
In the normoxic cat lung, N-nitro-L-arginine methyl ester (L-NAME) reduced the ID of all vessels observed, particularly 200-700 mum arteries, but L-canavaninecaused no ID change. The ID reduction was unaffected by ganglion blockade. The data suggest that continuous basal NO production by endothelial constitutive NO synthase (cNOS) contributes to the regulation of basal vascular tone of small pulmonary arteries and veins, particularly 200-700 arteries. Exogenous inhaled NO increased the ID of -200-700 mum arteries most strongly, suggesting that these vessels are most sensitive to NO.The dilator effect of endogenous
NO on the basal ID was about two or more times larger than the beta-adrenergic, cholinergic, or prostaglandin-mediated dilator effect. This suggests a very important role of NO in maintaining low basal pulmonary vascular tone.
In the cat lung exposed to acute hypoxia, L-NAME potentiated hypoxic ID reductions in 100-700 mum arteries and veins, suggesting that NO acts as an inhibitor for acute hypoxic pulmonary vasoconstriction. This suggestion was supported by the finding that exogenous NO could completely abolish the hypoxic ID reductions.
In the rat lung exposed to hypoxia for 2-3weeks, N-monomethyl-L-arginine caused significantly larger ID reductions than those for the control rat. The enhanced ID reduction was observed in smaller arteries (100-300 mum), but not in larger arteries (>300 mum). L-Canavanine reduced the ID in the hypoxic rat, but not in the control rat. The ID reduction was larger in the smaller arteries than in the larger arteries. The data suggest that NO generation by inducible NOS (iNOS) rather than cNOS inhibits vasoconstrictions of smaller arteries during the development of chronic hypoxic pulmonary hepertension. Less