Angiotensin II AT1 receptor blockade improves renal perfusion in hypercholesterolemia

Alejandro R. Chade, Martin G Rodriguez-Porcel, Steven J. Rippentrop, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Hypercholesterolemia (HC) is a risk factor for renal disease that may activate the angiotensin II type 1 (AT1) receptor and accelerate renal damage. Early diet-induced HC impairs renal perfusion responses, but it is yet unknown whether the AT1 receptor is involved. This study tested the hypothesis that AT1 receptor blockade improved renal perfusion and functional responses in hypercholesterolemic pigs. Methods: Regional renal hemodynamics and function in vivo were quantified bilaterally in pigs, at baseline and during vasoactive challenge (acetylcholine or sodium nitroprusside), using electron beam computed tomography after 12 weeks of normal (n = 6) or HC diet (n = 6), or HC diet supplemented (100 mg/d) with the AT1-receptor antagonist irbesartan (HC + AT1, n = 6). Results: Basal cortical and medullary perfusion was similar among the groups. Basal tubular function was similar on normal and HC diets, whereas HC + AT1 showed decreased proximal and distal fluid reabsorption. Hypercholesterolemic pigs had blunted cortical perfusion (P = .22) and augmented tubular responses to acetylcholine, whereas on HC + AT1 diet, cortical perfusion (P = .002) and tubular function were similar to normal animals. This was associated with decreased systemic levels of the oxidative stress markers thiobarbituric acid reactive substances. Conclusions: The AT1 receptor blockade in HC improves renal perfusion and tubular functional responses to endothelium-dependent vasodilators, in association with a decrease in oxidative stress. These results imply involvement of the renin-angiotensin system in the blunted renal cortical perfusion responses observed in HC, and suggest a potential role for these agents in preservation of intrarenal hemodynamics and function in HC.

Original languageEnglish (US)
Pages (from-to)111-115
Number of pages5
JournalAmerican Journal of Hypertension
Volume16
Issue number2
DOIs
StatePublished - Feb 1 2003

Fingerprint

Angiotensin Type 1 Receptor
Hypercholesterolemia
Angiotensin II
Perfusion
Kidney
Diet
Swine
irbesartan
Acetylcholine
Oxidative Stress
Hemodynamics
Angiotensin II Type 1 Receptor Blockers
Endothelium-Dependent Relaxing Factors
X Ray Computed Tomography
Thiobarbituric Acid Reactive Substances
Nitroprusside
Renin-Angiotensin System

Keywords

  • Angiotensin
  • Hypercholesterolemia
  • Regional blood flow
  • Tomography

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Angiotensin II AT1 receptor blockade improves renal perfusion in hypercholesterolemia. / Chade, Alejandro R.; Rodriguez-Porcel, Martin G; Rippentrop, Steven J.; Lerman, Amir; Lerman, Lilach O.

In: American Journal of Hypertension, Vol. 16, No. 2, 01.02.2003, p. 111-115.

Research output: Contribution to journalArticle

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