ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN HEMODYNAMIC ADAPTATIONS AFTER GRADED RENAL MASS REDUCTION

The mediator(s) of the adaptive increases in renal blood flow (RBF) an d glomerular filtration rate (GFR) after renal mass reduction have not been identified. The present studies were designed to investigate the role of endothelium-derived nitric oxide (EDNO) in the hemodynamic ad aptations after graded renal mass reduction. The experiments were perf ormed in rats that had undergone a sham reduction in renal mass, unine phrectomy (UNX), or 5/6 NX (UNX plus excision of both poles of the con tralateral kidney) 3-4 wk before. Measurements of RBF, GFR, renal vasc ular resistance (RVR), mean arterial pressure (MAP), and plasma renin concentration (PRC) were obtained before and after administration of t he EDNO synthesis inhibitor N(G)-monomethyl-L-arginine (L-NMMA). L-NMM A (50 mg/kg bolus plus 500 mug . kg-1 . min-1 infusion) led to signifi cant (P < 0.01) and comparable increases in MAP (mmHg) (P < 0.01) in s ham rats (117 +/- 6 to 154 +/- 6), UNX rats (112 +/- 5 to 139 +/- 7), and 5/6 NX rats (116 +/- 5 to 149 +/- 7). RVR increased significantly in all three groups (P < 0.01). The resultant decrease in RBF (ml . mi n-1 . kg-1) was similar in sham rats (34.9 +/- 2.6 to 23.8 +/- 1.6), U NX rats (43.9 +/- 3.6 to 27.3 +/- 2.8), and 5/6 NX rats (34.6 +/- 2 to 22.3 +/- 1.6) (P < 0.01 for all groups). Concomitant and significant (P < 0.01) decreases in GFR (ml. min-1 kg-1) were seen in sham rats (4 .8 +/- 0.5 to 3.5 +/- 0.5), UNX (6.4 +/- 0.4 to 4.9 +/- 0.4), and 5/6 NX rats (4.6 +/- 0.3 to 3.1 +/- 0.5). PRC decreased significantly in a ll groups after L-NMMA. RBF autoregulation was ''reset'' to a lower ba sal RBF, and autoregulatory efficiency was unchanged. Thus EDNO blocka de resulted in similar qualitative and quantitative effects on renal h emodynamics in sham, UNX, and 5/6 NX rats. These data do not provide s upport for a major role of EDNO in the hemodynamic adaptations after g raded renal mass reduction.