Renal injury in angiotensin II plus L-NAME-induced hypertensive rats is independent of elevated blood pressure

Polichnowski AJ, Lu L, Cowley A Jr. Renal injury in angiotensin II+L-NAME-induced hypertensive rats is independent of elevated blood pressure. Am J Physiol Renal Physiol 300: F1008-F1016, 2011. First published January 26, 2011; doi:10.1152/ajprenal.00354.2010.-The balance between angiotensin II (ANG II) and nitric oxide plays an important role in renal function and is thought to contribute to the progression of renal injury in experimental hypertension. In the present study, we investigated the extent of blood pressure (BP)dependent and BP-independent pathways of renal injury following 2 wk of hypertension produced by intravenous infusion of ANG II (5 ng.kg(-1).min(-1))+N-omega-nitro-L-arginine methyl ester (L-NAME; 1.4 mu g.kg(-1).min(-1)) in male Sprague-Dawley rats. An aortic balloon occluder was positioned between the renal arteries to maintain (24 h/day) BP to the left kidney (servo-controlled) at baseline levels, whereas the right kidney (uncontrolled) was chronically exposed to elevated BP. Over the 14-day experimental protocol, the average BP to uncontrolled kidneys (152.7 +/- 1.8 mmHg) was significantly elevated compared with servo-controlled (113.0 +/- 0.2 mmHg) kidneys and kidneys from sham rats (108.3 +/- 0.1 mmHg). ANG II+L-NAME infusion led to renal injury that was focal in nature and mainly confined to the outer medulla. Despite the differences in BP between servo-controlled and uncontrolled kidneys, there was a similar similar to 3.5-fold increase in renal outer medullary tubular injury, similar to 2-fold increase in outer medullary interstitial fibrosis, similar to 2-fold increase in outer medullary macrophage infiltration, and a significant increase in renal oxidative stress, all of which are indicative of BP-independent mediated pathways. The results of this study have important implications regarding the pathogenesis of renal injury in various experimental models of hypertension and provide novel insights regarding the variable association observed between hypertension and renal injury in some human populations.