Renoprotective effects of chronic candesartan treatment in uninephrectomized rat

Mahmood S Mozaffari, Kashyap B. Patel, Stephen W. Schaffer

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The authors recently observed an age-dependent reduction in the diuretic and natriuretic responses to plasma volume expansion in uninephrectomized control and glucose-intolerant rats. To determine the involvement of angiotensin II AT1 receptors in this phenomenon, the authors tested the hypothesis that chronic candesartan treatment preserves renal excretory function in the uninephrectomized rat. Control and glucose-intolerant rats underwent right nephrectomy at 4 weeks of age. Two weeks later, the animals in each group were further subdivided and maintained on tap water containing either candesartan cilexetil (10 mg · kg-1 · day-1) or vehicle. Renal excretory responses to acute extracellular fluid volume expansion (5% of body weight over 30 min) were determined in the 9-month-old conscious animal. Candesartan treatment markedly reduced the mean arterial pressure of controls and glucose-intolerant rats. Nonetheless, the baseline rates of fluid and electrolyte excretion, as well as the saline volume-induced diuretic, natriuretic, and kaliuretic responses, were greater in the candesartan-treated rats than in their vehicle-treated counterparts. The augmented baseline rates of fluid and sodium excretion in candesartan-treated rats were caused by a reduction in tubular reabsorption activity and an increase in glomerular filtration rate. However, the candesartan-mediated enhancement in saline volume-induced diuresis and natriuresis was caused by a reduction in tubular reabsorption activity. In addition to improving renal function, candesartan treatment reduced proteinuria in both groups. In conclusion, chronic blockade of the angiotensin II receptors exerts hypotensive and renoprotective effects in the aging uninephrectomized rat.

Original languageEnglish (US)
Pages (from-to)81-88
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume41
Issue number1
DOIs
StatePublished - Jan 1 2003

Fingerprint

Angiotensin Receptors
Kidney
Diuretics
Glucose
Angiotensin Type 1 Receptor
Natriuresis
Plasma Volume
Diuresis
Extracellular Fluid
candesartan
Nephrectomy
Glomerular Filtration Rate
Proteinuria
Electrolytes
Arterial Pressure
Sodium
Body Weight
Water
candesartan cilexetil

Keywords

  • Candesartan
  • Diuresis
  • Glucose intolerance
  • Natriuresis
  • Uninephrectomy

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Renoprotective effects of chronic candesartan treatment in uninephrectomized rat. / Mozaffari, Mahmood S; Patel, Kashyap B.; Schaffer, Stephen W.

In: Journal of Cardiovascular Pharmacology, Vol. 41, No. 1, 01.01.2003, p. 81-88.

Research output: Contribution to journalArticle

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