EFFECTS OF CHRONIC NITRIC-OXIDE SYNTHASE INHIBITION ON RENAL-FUNCTIONAND HISTOLOGY IN POLYCYTHEMIC RATS

Augmented endogenous nitric oxide (NO) production may ameliorate deran gement of renal functions or glomerular damage in polycythemia. To inv estigate this possibility, we examined the effect of NO synthase inhib ition with N-omega-nitro-L-arginine methyl ester (L-NAME; 50 mg/dl in drinking water) on renal functions and histology in heminephrectomized Sprague-Dawley rats treated for 4 weeks with recombinant human erythr opoietin (rh-EP; 500 IU/kg on alternate days). L-NAME elevated the blo od pressure which was aggravated by concomitant rh-EP and was ameliora ted by treatment with a nonpeptide angiotensin type 1 receptor blocker (CV116, 60 mg/kg in chow). The hematocrit level was prominently incre ased by rh-EP. The glomerular filtration rate was impaired by L-NAME a lone, but was maintained by concomitant administration of rh-EP or CV1 16. Micropuncture experiments revealed that the glomerular capillary p ressure was similarly elevated by L-NAME alone or in combination with rh-EP. L-NAME significantly, although not prominently, aggravated glom erular sclerosis observed with rh-EP alone, and concomitant CV116 amel iorated the glomerular damage. These results suggest that, in polycyth emia, enhanced NO production buffers the glomerular damage, and the ba lance between NO and angiotensin II may play an important role in main taining renal function and glomerular structure.