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OtherRENAL PHARMACOLOGY

Effects of the Novel Multiple-Action Agent Carvedilol on Severe Nephrosclerosis in Renal Ablated Rats

Jose C. Rodriguez-Perez, Antonio Losada, Aranzazu Anabitarte, Juan Cabrera, Javier Llobet, Leocadia Palop and Celia Plaza
Journal of Pharmacology and Experimental Therapeutics October 1997, 283 (1) 336-344;
Jose C. Rodriguez-Perez
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Antonio Losada
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Aranzazu Anabitarte
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Juan Cabrera
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Javier Llobet
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Leocadia Palop
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Celia Plaza
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Abstract

Antihypertensive drugs have differing effects on renal hemodynamics and morphology. We analyzed whether the use of a new betaadrenoceptor antagonist and vasodilator, carvedilol (CVD), slows the progression of nephrosclerosis and whether the renoprotective effect as well as reduction in cardiac hypertrophy is dependent on the degree of blood pressure reduction. Fifty-four adult male Sprague-Dawley rats were distributed among five groups: group I served as untreated controls with 5/6 nephrectomy (Nx); group II, sham (no renal ablation or drug treatment); group III, CVD 5 (5/6 Nx and treatment with oral CVD at 5 mg/kg/day); group IV, CVD 10 (5/6 Nx and treatment with oral CVD at 10 mg/kg/day); and group V, CVD 20 (5/6 Nx and treatment with oral CVD at 20 mg/kg/day). Tail-cuff blood pressure and 24-hr urine samples were obtained before and at 3, 5 and 11 weeks of treatment with CVD. At the end of the study period, blood was taken to measure serum creatinine, plasma renin activity and CVD levels, as well as the remnant kidney and heart for morphological studies. There was a significant reduction in 24-hr UProtV in all the CVD-treated groups, and it was increasingly evident with the highest dose used. However, only rats receiving doses of 10 and 20 mg/kg/day of CVD exhibited significant decreases in blood pressure. Elevated serum creatinine levels seen in untreated controls were significantly decreased by CVD in treated rats (P < .01), indicating that glomerular filtration rate was improved by this drug. This was associated with a significant increase in UNaV. Concomitant and significant (P < .01) decreases in plasma renin activity were observed in sham and CVD-treated rats. CVD-treated animals had considerably reduced renal damage (P < .01) and cardiac hypertrophy (P < .01) compared with untreated controls. These data indicate that CVD is effective in delaying progression of renal damage and provides beneficial effects in the remnant kidney and cardiac hypertrophy, even at nonhypotensive doses.

Footnotes

  • Send reprint requests to: Jose C. Rodriguez-Perez, M.D., Ph.D., Research Unit, Hospital Nuestra Señora del Pino, Angel Guimera, no. 93, 35005 Las Palmas de Gran Canaria, Spain. E-mail:jcrodrig{at}invest.hpino.rcanaria.es

  • ↵1 This work was supported in part by a grant from the Spanish Ministry of Health through Fondo de Investigación Sanitaria (FIS) 94/0331 (J.C.R.-P., A.L.) and by Boehringer-Mannheim (Spain). J.C.R.-P. was a visiting lecturer at the Brigham and Women’s Hospital, Boston, MA (FIS 91/5469), in 1992.

  • Abbreviations:
    CVD
    carvedilol
    DBP
    diastolic blood pressure
    GS
    glomerulosclerosis
    HPLC
    high-performance liquid chromatography
    MAP
    mean arterial pressure
    SBP
    systolic blood pressure
    UNaV
    urinary sodium excretion
    UKV
    urinary potassium excretion
    UV
    urinary flow
    UProtV
    urinary protein excretion
    Nx
    nephrectomy
    • Received January 2, 1997.
    • Accepted June 2, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
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1 Oct 1997
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OtherRENAL PHARMACOLOGY

Effects of the Novel Multiple-Action Agent Carvedilol on Severe Nephrosclerosis in Renal Ablated Rats

Jose C. Rodriguez-Perez, Antonio Losada, Aranzazu Anabitarte, Juan Cabrera, Javier Llobet, Leocadia Palop and Celia Plaza
Journal of Pharmacology and Experimental Therapeutics October 1, 1997, 283 (1) 336-344;

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OtherRENAL PHARMACOLOGY

Effects of the Novel Multiple-Action Agent Carvedilol on Severe Nephrosclerosis in Renal Ablated Rats

Jose C. Rodriguez-Perez, Antonio Losada, Aranzazu Anabitarte, Juan Cabrera, Javier Llobet, Leocadia Palop and Celia Plaza
Journal of Pharmacology and Experimental Therapeutics October 1, 1997, 283 (1) 336-344;
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