Renal dysfunction after chronic blockade of nitric oxide synthesis.
The effects of the chronic inhibition of nitric oxide (NO) on renal hemodynamics and tubular function were studied in rats treated for 8 weeks with the NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg/day). In addition, the effect of L-NAME administration on vasoactive systems (renin-angiotensin system, aldosterone, catecholamines, endothelin, and thromboxane A(2)) was evaluated. Chronic inhibition of NO significantly elevated blood pressure, reduced glomerular filtration rate and renal blood flow, blunted the pressure-diuresis-natriuresis response, and increased protein urine excretion. All these changes were associated with blunted nitrite production in response to acetylcholine in glomeruli. No changes were observed in the plasma levels of either renin activity, aldosterone, or endothelin in L-NAME-treated rats. Similarly, no differences were observed in the urinary excretion of thromboxane B(2) between both group of animals. By contrast, plasma concentrations of both epinephrine and norepinephrine were elevated in rats treated with L-NAME. In summary, the results show that chronic blockade of NO produced not only alterations in renal function, but also renal damage, suggesting an important renoprotective role of NO. An activation of sympathoadrenal system could participate in these renal alterations.
Cachofeiro
Victoria
V
Departamentos de Fisiología, Facultades de Medicina, Universidad Complutense de Madrid, Spain. vcara@med.ucm.es
Fortepiani
Lourdes A
LA
Navarro-Cid
Josefa
J
Lahera
Vicente
V
García-Estañ
Joaquín
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009573:Nitrites / Q000652:urine; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D009573:Nitrites; D009569:Nitric Oxide; D003404:Creatinine; D019331:NG-Nitroarginine Methyl Ester