Characterization of the renal action of pranidipine in the rat

Takahiko Nagahama, Koichi Hayashi, Keiji Fujiwara, Yuri Ozawa, Takao Saruta

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Although calcium antagonists elicit predominant dilation of afferent arterioles that might be associated with glomerular hypertension, there have been reported diverse observations demonstrating the effect of calcium antagonists on the progression of renal injury. The present study examined the effect of pranidipine (CAS 99522-79-9) on the renal microvascular tone in the isolated perfused hydronephrotic rat kidney, and the progression of renal insufficiency in subtotally nephrectomized spontaneously hypertensive rats. In the hydronephrotic kidney, angiotensin II caused marked constriction of both afferent and efferent arterioles. The subsequent addition of pranidipine (10 nmol/l, 100 nmol/l, 1 μmol/l) elicited dose-dependent afferent arteriolar dilation, with 97 ± 3 % reversal at 1 μmol/l. In contrast, efferent arterioles were resistant to pranidipine, with only 20 ± 4 % reversal at 1 μmol/l. In subtotally nephrectomized rats, 10-week treatment with pranidipine (3.0 mg/kg/day) markedly decreased blood pressure (from 270 ± 6 to 158 ± 8 mmHg) and improved renal histopathological changes, including glomerular and arteriolar sclerosis. Proteinuria was also less than than in the control rats (233 ± 5 vs. 305 ± 26 mg/day). Thus, although glomerular hypertension might develop as a consequence of preferential afferent arteriolar dilation, pranidipine actually improved the renal injury in subtotally nephrectomized SHR. These ostensibly discrepant observations could be attributed to the simultaneous reduction in blood pressure and the salutary actions of this agent mediated by non-hemodynamic mechanisms.

Original languageEnglish
Pages (from-to)248-253
Number of pages6
JournalArzneimittel-Forschung/Drug Research
Volume50
Issue number3
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • CAS 99522-79-9
  • Calcium antagonist
  • Pranidipine
  • Rat
  • Renal microvascular effect

ASJC Scopus subject areas

  • Drug Discovery

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