alexa Characterization of the renal action of pranidipine in the rat.
Surgery

Surgery

Medical & Surgical Urology

Author(s): Nagahama T, Hayashi K, Fujiwara K, Ozawa Y, Saruta T

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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 mumol/l) elicited dose-dependent afferent arteriolar dilation, with 97 +/- 3\% reversal at 1 mumol/l. In contrast, efferent arterioles were resistant to pranidipine, with only 20 +/- 4\% reversal at 1 mumol/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. This article was published in Arzneimittelforschung and referenced in Medical & Surgical Urology

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