(Circulation. 1995;92:3105-3112.)
© 1995 American Heart Association, Inc.
Articles |
Expression of Renin-Angiotensin System Components in the Heart, Kidneys, and Lungs of Rats With Experimental Heart Failure
From the Hypertension-Endocrine Branch (Z.A.A., H.R.K.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md; and Centro di Fisiologia Clinica e Ipertensione (F.P.), Ospedale Maggiore, Universita' di Milano, Italy.
Correspondence to Zaid A. Abassi, PhD, Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, Bldg 10, Room 8C103, 10 Center Drive, MSC-1754, Bethesda, MD 20892-1754.
Background Chronic activation of the renin-angiotensin system (RAS) plays an important role in the pathogenesis of heart failure. Increasing evidence indicates that other than the circulating RAS, a local RAS exists in several tissues, including the heart. The present study was carried out to quantify cardiac, renal, and pulmonary mRNA levels of renin, angiotensin-converting enzyme (ACE), and types 1 and 2 angiotensin II receptors (AT-1 and AT-2), in rats with different severities of heart failure.
Methods and Results Heart failure was induced by the creation of an aortocaval fistula below the renal arteries. Rats with aortocaval fistula either compensate and maintain a normal sodium balance or decompensate and develop severe sodium retention. Six days after placement of the aortocaval fistula, heart weight (normalized to body weight) increased 35% (P<.05) in compensated and 65% in decompensated rats compared with control rats. Plasma renin activity increased 45% (P<.05) in rats in sodium balance and 127% in sodium-retaining rats. Total RNA was extracted from the heart, kidneys, and lungs, followed by reverse transcription–quantitative polymerase chain reaction. Renin mRNA levels in the heart, after 40 cycles, increased 68% (P<.01) and 140% in rats with either compensated or decompensated heart failure, respectively. Renal renin-mRNA levels also increased 130% (P<.05) in decompensated and only 52% (P<.05) in compensated animals. ACE-mRNA increased in a similar pattern in the heart but not in either the kidneys or lungs. Moreover, pulmonary, renal, and cardiac ACE immunoreactivity levels, assessed by Western blot analysis, showed the same trend. AT-1 receptor mRNA levels decreased 54% (P<.05) only in the myocardium of decompensated rats, whereas AT-2 receptor mRNA did not change in any tissue studied.
Conclusions The development of heart failure is associated with a remarkable increase in the expression of a local RAS in the heart, which may contribute to the pathogenesis of this clinical syndrome.
Key Words: heart failure • renin-angiotensin system
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