Hemodynamic basis for the limited renal injury in rats with angiotensin II-induced hypertension

Am J Physiol Renal Physiol. 2015 Feb 1;308(3):F252-60. doi: 10.1152/ajprenal.00596.2014. Epub 2014 Dec 4.

Abstract

ANG II is thought to increase the susceptibility to hypertension-induced renal disease (HIRD) via blood pressure (BP)-dependent and BP-independent pathways; however, the quantitative relationships between BP and HIRD have not been examined in ANG II-infused hypertensive rats. We compared the relationship between radiotelemetrically measured BP and HIRD in Sprague-Dawley rats (Harlan) chronically administered ANG II (300-500 ng·kg(-1)·min(-1), n = 19) for 4 wk versus another commonly employed pharmacological model of hypertension induced by the chronic administration of N(ω)-nitro-l-arginine methyl ester (l-NAME, 50 mg·kg(-1)·day(-1), n = 23). [DOSAGE ERROR CORRECTED]. Despite the significantly higher average systolic BP associated with ANG II (191.1 ± 3.2 mmHg) versus l-NAME (179.9 ± 2.5 mmHg) administration, the level of HIRD was very modest in the ANG II versus l-NAME model as evidenced by significantly less glomerular injury (6.6 ± 1.3% vs. 11.3 ± 1.5%, respectively), tubulointerstitial injury (0.3 ± 0.1 vs. 0.7 ± 0.1 injury score, respectively), proteinuria (66.3 ± 10.0 vs. 117.5 ± 10.1 mg/day, respectively), and serum creatinine levels (0.5 ± 0.04 vs. 0.9 ± 0.07 mg/dl, respectively). Given that HIRD severity is expected to be a function of renal microvascular BP transmission, BP-renal blood flow (RBF) relationships were examined in additional conscious rats administered ANG II (n = 7) or l-NAME (n = 8). Greater renal vasoconstriction was observed during ANG II versus l-NAME administration (41% vs. 23% decrease in RBF from baseline). Moreover, administration of ANG II, but not l-NAME, led to a unique BP-RBF pattern in which the most substantial decreases in RBF were observed during spontaneous increases in BP. We conclude that the hemodynamic effects of ANG II may mediate the strikingly low susceptibility to HIRD in the ANG II-infused model of hypertension in rats.

Keywords: Nω-nitro-l-arginine methyl ester; blood pressure; radiotelemetry; renal blood flow.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Angiotensin II / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Hemodynamics / drug effects*
  • Hypertension / chemically induced*
  • Kidney / blood supply
  • Kidney / drug effects*
  • Male
  • Rats, Sprague-Dawley
  • Renal Circulation / drug effects

Substances

  • Angiotensin II