NITRIC-OXIDE MEDIATES RENAL VASODILATION DURING ERYTHROPOIETIN-INDUCED POLYCYTHEMIA

The renal blood flow (RBF) of patients with polycythemia rubra vera is increased despite the high hematocrit (Hct) which elevates the whole blood viscosity. Since blood viscosity determines the shear force on t he endothelium which is a major stimulus to nitric oxide (NO) release, we investigated the hypothesis that renal vasodilation during erythro poietin-induced erythrocytosis is mediated by the L-arginine-NO pathwa y. Groups of Sprague-Dawley rats received thrice weekly injections of erythropoietin (E) for two to five weeks; responses were contrasted wi th normal rats (N) which received sham injections. The first group was studied after five weeks of erythropoietin injections which led to sh arp increases in Hct (E: 72 +/- 3 vs. N: 44 +/- 1%) and mean arterial pressure (MAP: 126 +/- 3 vs. 107 +/- 3 mm Hg). These rats had an eleva ted basal RBF whether measured by the clearance and renal extraction o f PAH or by a transit-time renal blood flow meter. Subsequent groups w ere studied after two to three weeks of erythropoietin which raised th e Hct more modestly to 59 +/- 2%. In this group, the basal MAP was sim ilar in E and N rats. Graded doses of the NO synthase inhibitor, N(ome ga)monomethyl-L-arginine (L-NMA) led to a steeper rise in MAP in E tha n N; at the highest doses, the MAP had increased by 36 +/- 2 in E and 23 +/- 3 mm Hg in N (P < 0.01). Therefore, to assess the effects of L- NMA on renal vascular resistance without the confounding effects of di fferences in MAP, the renal perfusion pressure (RPP) was controlled wi th a suprarenal aortic clamp. In the basal state, the RBF was higher i n E than N (E: 5.33 +/- 0.54 vs. N: 3.85 +/- 0.28 ml - min-1 . 100 g-1 ; P < 0.025). L-NMA caused a greater reduction in RBF, and a greater r ise in filtration fraction (FF) and renal vascular resistance (RVR) in erythropoietin-treated rats. During L-NMA, the RBF became similar in the two groups (E: 2.19 +/- 0.50 vs. N: 2.42 +/-0.32 ml . min-1 . 100 g-1; NS). We conclude that an enhanced generation of NO from L-arginin e maintains normotension and mediates renal vasodilation in rats with erythropoietin-induced erythrocytosis.