Effects of chronic nitric oxide synthase inhibition on renal function and histology in polycythemic rats.
Augmented endogenous nitric oxide (NO) production may ameliorate derangement of renal functions or glomerular damage in polycythemia. To investigate this possibility, we examined the effect of NO synthase inhibition 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 erythropoietin (rh-EP; 500 IU/kg on alternate days). L-NAME elevated the blood pressure which was aggravated by concomitant rh-EP and was ameliorated by treatment with a nonpeptide angiotensin type 1 receptor blocker (CV116; 60 mg/kg in chow). The hematocrit level was prominently increased by rh-EP. The glomerular filtration rate was impaired by L-NAME alone, but was maintained by concomitant administration of rh-EP or CV116. Micropuncture experiments revealed that the glomerular capillary pressure was similarly elevated by L-NAME alone or in combination with rh-EP. L-NAME significantly, although not prominently, aggravated glomerular sclerosis observed with rh-EP alone, and concomitant CV116 ameliorated the glomerular damage. These results suggest that, in polycythemia, enhanced NO production buffers the glomerular damage, and the balance between NO and angiotensin II may play an important role in maintaining renal function and glomerular structure.
Kawata
T
T
Department of Medicine II, Hokkaido University School of Medicine, Japan.
Hashimoto
S
S
Koike
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011086:Polycythemia / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D011355:Prodrugs / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D011355:Prodrugs; D011994:Recombinant Proteins; D013777:Tetrazoles; D004921:Erythropoietin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C077793:candesartan cilexetil; D019331:NG-Nitroarginine Methyl Ester