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Effect of angiotensin II type 1 receptor blockade on conduit artery tone in subtotally nephrectomized rats

Peeter Kööbi1, Pasi Jolma, Jarkko Kalliovalkama

  • 1Department of Pharmacological Sciences, Medical School, University of Tamperel, Tampere, Finland. peeter.koobi@uta.fi

Nephron. Physiology
|April 2, 2004
PubMed
Abstract

Insights

Losartan treatment improved large artery function in rats with renal failure by reducing vasoconstriction and enhancing vasorelaxation. This AT1 receptor blockade offers benefits to conduit arteries, even without changes in blood pressure or kidney function.

Area of Science:

  • Cardiovascular Physiology
  • Renal Medicine
  • Pharmacology

Background:

  • Angiotensin II type 1 (AT1) receptor antagonists improve organ protection and resistance artery function in uremia.
  • The impact of AT1 blockade on conduit artery function in renal failure remains unclear.

Purpose of the Study:

  • To investigate the effect of losartan, an AT1 receptor antagonist, on conduit artery function in a rat model of renal failure.

Main Methods:

  • 8-week losartan therapy in 5/6 nephrectomized (NX) rats.
  • Assessment of isolated mesenteric arterial ring tone.
  • Measurement of blood and urine chemistry.
  • Quantification of renal AT1 receptors via autoradiography.

Main Results:

  • NX rats exhibited reduced creatinine clearance but stable blood pressure.
  • Losartan prevented [125I]-Sar1,Ile8-angiotensin II binding to renal AT1 receptors.
  • Losartan attenuated endothelin-1-induced vasoconstriction in both NX and Sham rats.
  • Acetylcholine-induced vasorelaxation was impaired in untreated NX rats but preserved in losartan-treated NX rats.
  • Levcromakalim-induced vasorelaxation was impaired in untreated NX rats but normalized with losartan treatment.

Conclusions:

  • AT1 receptor blockade with losartan reduces vasoconstriction and enhances K+ channel-mediated vasorelaxation in large arteries of rats with renal failure.
  • These functional benefits occur independently of changes in blood pressure or renal function.
  • AT1 blockade confers significant functional advantages to conduit arteries in the context of renal failure.

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