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
Publication statusPublished - 2000

Fingerprint

Rats
Kidney
Arterioles
Blood pressure
Dilatation
Rat control
Arteriolosclerosis
Calcium
Blood Pressure
Hypertension
Angiotensin II
Wounds and Injuries
Inbred SHR Rats
Proteinuria
Constriction
Renal Insufficiency
pranidipine

Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Pharmacology

Cite this

Nagahama, T., Hayashi, K., Fujiwara, K., Ozawa, Y., & Saruta, T. (2000). Characterization of the renal action of pranidipine in the rat. Arzneimittel-Forschung/Drug Research, 50(3), 248-253.

Characterization of the renal action of pranidipine in the rat. / Nagahama, Takahiko; Hayashi, Koichi; Fujiwara, Keiji; Ozawa, Yuri; Saruta, Takao.

In: Arzneimittel-Forschung/Drug Research, Vol. 50, No. 3, 2000, p. 248-253.

Research output: Contribution to journalArticle

Nagahama, T, Hayashi, K, Fujiwara, K, Ozawa, Y & Saruta, T 2000, 'Characterization of the renal action of pranidipine in the rat', Arzneimittel-Forschung/Drug Research, vol. 50, no. 3, pp. 248-253.
Nagahama T, Hayashi K, Fujiwara K, Ozawa Y, Saruta T. Characterization of the renal action of pranidipine in the rat. Arzneimittel-Forschung/Drug Research. 2000;50(3):248-253.
Nagahama, Takahiko ; Hayashi, Koichi ; Fujiwara, Keiji ; Ozawa, Yuri ; Saruta, Takao. / Characterization of the renal action of pranidipine in the rat. In: Arzneimittel-Forschung/Drug Research. 2000 ; Vol. 50, No. 3. pp. 248-253.
@article{c61a2535a27d42ca8e17376edf6e9361,
title = "Characterization of the renal action of pranidipine in the rat",
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.",
keywords = "Calcium antagonist, CAS 99522-79-9, Pranidipine, Rat, Renal microvascular effect",
author = "Takahiko Nagahama and Koichi Hayashi and Keiji Fujiwara and Yuri Ozawa and Takao Saruta",
year = "2000",
language = "English",
volume = "50",
pages = "248--253",
journal = "Drug Research",
issn = "2194-9379",
publisher = "Thieme",
number = "3",

}

TY - JOUR

T1 - Characterization of the renal action of pranidipine in the rat

AU - Nagahama, Takahiko

AU - Hayashi, Koichi

AU - Fujiwara, Keiji

AU - Ozawa, Yuri

AU - Saruta, Takao

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Calcium antagonist

KW - CAS 99522-79-9

KW - Pranidipine

KW - Rat

KW - Renal microvascular effect

UR - http://www.scopus.com/inward/record.url?scp=0034121431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034121431&partnerID=8YFLogxK

M3 - Article

C2 - 10758776

AN - SCOPUS:0034121431

VL - 50

SP - 248

EP - 253

JO - Drug Research

JF - Drug Research

SN - 2194-9379

IS - 3

ER -