Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat

Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2537-42. doi: 10.1152/ajpheart.01081.2006. Epub 2007 Aug 10.

Abstract

Obesity is an emerging risk factor for renal dysfunction, but the mechanisms are poorly understood. Obese patients show heightened renal vasodilation to blockade of the renin-angiotensin system, suggesting deficits in vascular responses to angiotensin II (ANG II). This study tested the hypothesis that obesity augments renal vasoconstriction to ANG II. Lean (LZR), prediabetic obese (OZR), and nonobese fructose-fed Zucker rats (FF-LZR) were studied to determine the effects of obesity and insulin resistance on reactivity of blood pressure and renal blood flow to vasoconstrictors. OZR showed enlargement of the kidneys, elevated urine output, increased sodium intake, and decreased plasma renin activity (PRA) vs. LZR, and renal vasoconstriction to ANG II was augmented in OZR. Renal reactivity to norepinephrine and mesenteric vascular reactivity to ANG II were similar between LZR and OZR. Insulin-resistant FF-LZR had normal reactivity to ANG II, indicating the insulin resistance was an unlikely explanation for the changes observed in OZR. Four weeks on a low-sodium diet (0.08%) to raise PRA reduced reactivity to ANG II in OZR back to normal levels without effect on LZR. From these data, we conclude that in the prediabetic stages of obesity, a decrease in PRA is observed in Zucker rats that may lead to increased renal vascular reactivity to ANG II. This increased reactivity to ANG II may explain the elevated renal vasodilator effects observed in obese humans and provide insight into early changes in renal function that predispose to nephropathy in later stages of the disease.

Publication types

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

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin II / pharmacology
  • Animals
  • Blood Pressure
  • Diet, Sodium-Restricted
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Heart Rate
  • Insulin Resistance
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism
  • Kidney Diseases / physiopathology*
  • Kidney Diseases / prevention & control
  • Mesenteric Artery, Superior / metabolism
  • Mesenteric Artery, Superior / physiopathology
  • Norepinephrine / pharmacology
  • Obesity / complications*
  • Obesity / diet therapy
  • Obesity / metabolism
  • Obesity / physiopathology
  • Prediabetic State / complications*
  • Prediabetic State / diet therapy
  • Prediabetic State / metabolism
  • Prediabetic State / physiopathology
  • Rats
  • Rats, Zucker
  • Renal Artery / drug effects
  • Renal Artery / metabolism
  • Renal Artery / physiopathology*
  • Renal Circulation* / drug effects
  • Renin / blood
  • Renin-Angiotensin System
  • Vasoconstriction* / drug effects
  • Vasoconstrictor Agents / metabolism*
  • Vasoconstrictor Agents / pharmacology

Substances

  • Vasoconstrictor Agents
  • Angiotensin II
  • Renin
  • Norepinephrine