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Role of cardiac renin-angiotensin system in the development of pressure-overload left ventricular hypertrophy in rats with abdominal aortic constriction

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Abstract

Possible involvement of cardiac renin-angiotensin system (RAS) in pressure overload induced left ventricular hypertrophy (LVH) was investigated. Rats were subjected to abdominal aortic constriction (AAC) and examined the effects of 4 weeks treatments with an angiotensin converting enzyme (ACE) inhibitor, captopril and a vasodilator, hydralazine on haemodynamics and ventricular RNA, DNA, protein and myosin isoform pattern in sham and hypertrophied rats. AAC increased the mean arterial pressure (MAP) and systolic blood pressure (SBP), and resulted in increased left ventricle/body weight ratio, LV thickness, RNA and protein content, however total DNA was not changed. The expression of fetal isogene, β-myosin heavy chain (β-MHC), was markedly enhanced where as u.-MHC was reduced. High-dose captopril (100 mg/kg p.o.,) significantly prevented the increase in haemodynamics, development of LVH, LV remodeling, increase in total protein, RNA and antithetical expression of myosin isoforms. Hydralazine (15 mg/kg p.o.,), did not modulate hypertrophic changes and low-dose captopril (1.5 mg/kg p.o.,) which has not produced any marked fall in MAP and SBP also modulated favourably the development of LVH and its biochemical markers. Thus, the prevention of the development of LVH and induction of β-MHC by non-hypotensive doses of captopril may be related to the blockade of intracardiac production of angiotensin II rather than circulating system. These results suggest that cardiac RAS may play an important role in pressure overload induced LVH.

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Authors and Affiliations

  1. Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, 160 014, Chandigarh, India

    Doodipala S. Reddy & Manjeet Singh

  2. Department of Experimental Medicine, Post Graduate Institute of Medical Education and Research, 160 012, Chandigarh, India

    Sujata Ghosh & N. K. Ganguly

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  1. Doodipala S. Reddy
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  2. Manjeet Singh
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  3. Sujata Ghosh
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  4. N. K. Ganguly
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Reddy, D.S., Singh, M., Ghosh, S. et al. Role of cardiac renin-angiotensin system in the development of pressure-overload left ventricular hypertrophy in rats with abdominal aortic constriction. Mol Cell Biochem 155, 1–11 (1996). https://doi.org/10.1007/BF00714327

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  • DOI: https://doi.org/10.1007/BF00714327

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