ENDOTHELIUM-DERIVED NITRIC-OXIDE REDUCES BASE-LINE VENOUS TONE IN AWAKE INSTRUMENTED RATS

To determine whether nitric oxide, which is likely endothelium-derived relaxing factor (EDRF), modulates baseline venous tone, the effects o f intravenous N(G)-monomethyl-L-arginine (L-NMMA) (3-25 mg/kg), an EDR F inhibitor, on mean circulatory filling pressure (MCFP) were determin ed in 10 awake instrumented rats. MCFP, the equilibrated systemic pres sure occurring when the circulation is arrested by transient inflation of a balloon in the right atrium, is a measure of total venous capaci tance. L-NMMA caused a dose-dependent increase in mean arterial pressu re and a dose-dependent decrease in heart rate. MCFP rose from 6.6 +/- 0.2 to 7.6 +/- 0.2 mmHg at the highest L-NMMA dose. The effects of L- NMMA on MCFP were reversed with L-arginine. In an additional four rats , in which hexamethonium was administered to induce ganglionic blockad e, L-NMMA (25 mg/kg) caused a similar increase in MCFP (4.1 +/- 0.6 to 5.0 +/- 0.7 mmHg, P = 0.22) during the ganglionic blocked state as du ring the control unblocked state. These findings suggest that nitric o xide, which is likely EDRF, reduces baseline venous tone.