ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN THE REGULATION OF TONUS IN LARGE-BORE ARTERIAL RESISTANCE VESSELS, ARTERIOLES AND VEINS IN CAT SKELETAL-MUSCLE

The role of endothelium-derived nitric oxide in the regulation of vascular resistance (tonus) in cat skeletal muscle with the use of N(G)-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide formation from L-arginine. The study was performed with a whole-organ technique which permits simultaneous, continuous and quantitative recordings of resistance reactions in the whole vascular bed (R(T)) and in its three consecutive sections: large-bore arterial resistance vessels (>25 μm; R(a, prox)), small arterioles (<25 μm; R(a, micro)) and veins (R(v)). N(G)-monomethyl-L-arginine (3-100 mg kg-1 tissue, i.a.) induced a dose-dependent increase in resistance that was preferentially, but not selectively, confined to the large-bore arterial resistance vessels. At a maximally effective dose (100 mg kg-1), the nitric oxide inhibitor caused a marked constriction, within 5 min, on average increasing R(T) by 99%, R(a, prox) by 138%, R(a, micro) by 18% and R(v) by 23%. The constrictor response to N(G)-monomethyl-L-arginine was long-lasting but disappeared gradually over a period of about 1 h. However, it could be abruptly abolished by excess L-arginine (300 mg kg-1, i.a.). The vasodilator response (R(T)) to acetylcholine was significantly attenuated in the presence of N(G)-monomethyl-L-arginine compared with the control response. The results suggested that nitric oxide formation from L-arginine by the vascular endothelium plays a fundamental role in the regulation of vascular resistance (tone) in vivo, with its main site of action located in the large-bore arterial resistance vessels.