Regulation of oxygen utilization by angiotensin II in chronic kidney disease.
Angiotensin II blockade delays progression of chronic kidney disease by modifying intrarenal hemodynamics, but the effects on metabolic adaptations are unknown. Using the remnant kidney model of chronic kidney disease in rats, we measured the effects of combined angiotensin II blockade with captopril and losartan on renal oxygen consumption (QO(2)) and factors influencing QO(2). Remnant kidneys had proteinuria and reductions in the glomerular filtration rate (GFR), renal blood flow (RBF) and nitric oxide synthase-1 protein expression while QO(2), factored by sodium reabsorption (QO(2)/TNa), was markedly increased. Combined blockade treatment normalized these parameters while increasing sodium reabsorption but, since QO(2) was unchanged, QO(2)/TNa also normalized. Triple antihypertensive therapy, to control blood pressure, and treatment with lysine, to increase GFR and RBF, did not normalize QO(2)/TNa, suggesting a specific effect of angiotensin II in elevating QO(2)/TNa. Inhibition of nitric oxide synthase increased QO(2) in the kidney of sham-operated rats but not in the remnant kidney of untreated rats. Our study shows that combined captopril and losartan treatment normalized QO(2)/TNa and functional nitric oxide activity in the remnant kidney independent of blood pressure and GFR effects, suggesting that other mechanisms in addition to hemodynamics underlie the benefits of angiotensin II blockade.
Deng
Aihua
A
Division of Nephrology-Hypertension, Department of Medicine, School of Medicine, University of California, San Diego, San Diego, California 92161, USA. adeng@ucsd.edu
Tang
Tong
T
Singh
Prabhleen
P
Wang
Chen
C
Satriano
Joe
J
Thomson
Scott C
SC
Blantz
Roland C
RC
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004195:Disease Models, Animal; D007674:Kidney Diseases / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption; D051381:Rats; D012964:Sodium / Q000378:metabolism
D000804:Angiotensin II; D002216:Captopril; D012964:Sodium; D019001:Nitric Oxide Synthase; D019808:Losartan