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OtherCARDIOVASCULAR PHARMACOLOGY

Beneficial Effects of Long-term Enalapril Treatment and Low-Salt Intake on Survival Rate of Dahl Salt-Sensitive Rats with Established Hypertension

Kohtarou Kodama, Hideyuki Adachi and Jiro Sonoda
Journal of Pharmacology and Experimental Therapeutics November 1997, 283 (2) 625-629;
Kohtarou Kodama
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Hideyuki Adachi
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Jiro Sonoda
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Abstract

We investigated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor enalapril and low-salt intake on the survival rate of Dahl salt-sensitive rats fed a high-salt (6.0% NaCl) diet. The systolic blood pressure of the rats increased gradually from 5 weeks of age and reached >240 mm Hg at 12 weeks of age. At this point, a low-salt diet group received a placebo (group 1,n = 10), and the high-salt diet group was divided into three groups: those given a placebo with the high-salt diet (group 2, n = 15), those given a chow change from a high- to a low-salt diet with a placebo (group 3, n = 14) and those given enalapril (30 mg/kg/day p.o., group 4,n = 14). At 19 weeks of age, all rats in group 1 were alive, and the survival rate of group 2 was only 40% (P < .001 vs. group 1). The survival rates of both groups 3 and 4 were significantly better: 86% (P < .01 vs.group 2) and 93% (P < .01), respectively. This beneficial effect on mortality was accompanied by an amelioration of the elevated plasma creatinine and urea nitrogen levels and a decrease in the glomerular sclerosis lesion scores in both groups. These results suggested that a high-salt content diet and the renin-angiotensin system are deterioration factors in lethal renal damage and the limitation of the diet salt content and inhibition of the renin-angiotensin system are important to improve the survival rate in high-salt-loaded hypertensive Dahl salt-sensitive rats.

Footnotes

  • Send reprint requests to: Dr. Kohtarou Kodama, Cardiovascular Research Unit, Tsukuba Research Laboratories, Eisai Co., Ltd., 1–3, Tokodai 5-Choume, Tsukuba, Ibaraki 300–26, Japan.

  • Abbreviations:
    DS
    Dahl salt-sensitive
    ACE
    angiotensin-converting enzyme
    Ang II
    angiotensin II
    SBP
    systolic blood pressure
    HR
    heart rate
    • Received January 29, 1997.
    • Accepted July 23, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 283, Issue 2
1 Nov 1997
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OtherCARDIOVASCULAR PHARMACOLOGY

Beneficial Effects of Long-term Enalapril Treatment and Low-Salt Intake on Survival Rate of Dahl Salt-Sensitive Rats with Established Hypertension

Kohtarou Kodama, Hideyuki Adachi and Jiro Sonoda
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 625-629;

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OtherCARDIOVASCULAR PHARMACOLOGY

Beneficial Effects of Long-term Enalapril Treatment and Low-Salt Intake on Survival Rate of Dahl Salt-Sensitive Rats with Established Hypertension

Kohtarou Kodama, Hideyuki Adachi and Jiro Sonoda
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 625-629;
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