EXPRESSION OF RENIN-ANGIOTENSIN SYSTEM COMPONENTS IN THE HEART, KIDNEYS, AND LUNGS OF RATS WITH EXPERIMENTAL HEART-FAILURE

Background Chronic activation of the renin-angiotensin system (RAS) pl ays an important role in the pathogenesis of heart failure. Increasing evidence indicates that other than the circulating RAS, a local RAS e xists in several tissues, including the heart. The present study was c arried out to quantify cardiac, renal, and pulmonary mRNA levels of re nin, angiotensin-converting enzyme (ACE), and types 1 and 2 angiotensi n II receptors (AT-1 and AT-2), in rats with different severities of h eart failure. Methods and Results Heart failure was induced by the cre ation of an aortocaval fistula below the renal arteries. Rats with aor tocaval fistula either compensate and maintain a normal sodium balance or decompensate and develop severe sodium retention. Six days after p lacement of the aortocaval fistula, heart weight (normalized to body w eight) increased 35% (P<.05) in compensated and 65% in decompensated r ats compared with control rats. Plasma renin activity increased 45% (P <.05) in rats in sodium balance and 127% in sodium-retaining rats. Tot al RNA was extracted from the heart, kidneys, and lungs, followed by r everse transcription-quantitative polymerase chain reaction. Renin mRN A levels in the heart, after 40 cycles, increased 68% (P<.01) and 140% in rats with either compensated or decompensated heart failure, respe ctively. Renal renin-mRNA levels also increased 130% (P<.05) in decomp ensated and only 52% (P<.05) in compensated animals. ACE-mRNA increase d in a similar pattern in the heart but not in either the kidneys or l ungs. Moreover, pulmonary, renal, and cardiac ACE immunoreactivity lev els, assessed by Western blot analysis, showed the same trend. AT-1 re ceptor mRNA levels decreased 54% (P<.05) only in the myocardium of dec ompensated rats, whereas AT-2 receptor mRNA did not change in any tiss ue studied. Conclusions The development of heart failure is associated with a remarkable increase in the expression of a local RAS in the he art, which may contribute to the pathogenesis of this clinical syndrom e.