Endothelium-derived nitric oxide is less important for basal tone regulation in the pulmonary than the renal circulation of the adult rat

Inhibition of endothelium-derived nitric oxide (EDNO) synthesis causes systemic hypertension. The effects of EDNO inhibition on vascular tone in the low-pressure pulmonary circuit are more controversial. This study tested the hypothesis that basal EDNO synthesis plays a less important role in determining resting tone in the lung than in the kidney. To permit a simultaneous comparison of the renal and pulmonary circulations, independent of the effects of prostaglandins and blood elements, we developed a new model in which isolated kidney was perfused in series with lung from the same rat using blood-free albumin perfusate containing meclofenamate. The competitive EDNO synthesis inhibitors, N(ω)-nitro-L-arginine and N(ω)-nitro-L-arginine methyl ester (up to 1.5 μM), more than doubled perfusion pressure in the kidneys but had no effect on perfusion pressure in the lungs. In addition, both blockers enhanced the slope of the perfusion pressure-flow relation in kidneys but not in lungs. Renal vasoconstriction induced by arginine analogues was reversed by the EDNO precursor L-arginine. We conclude that EDNO is an important basal tone regulator in the renal circulation, but is not the primary determinant of the low basal pulmonary vascular tone in the normal adult rat. Increases in flow do not trigger functionally significant EDNO release in the lung. Interorgan differences in the functional significance of EDNO may have therapeutic implications.