TISSUE EXPRESSION OF COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM IN EXPERIMENTAL POSTINFARCTION HEART-FAILURE IN RATS - EFFECTS OF HEART-FAILURE AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR TREATMENT

1. It has been suggested that local tissue renin-angiotensin systems m ay be activated in heart failure and that effects on such systems may, at least partially explain the beneficial effects of angiotensin-conv erting enzyme (ACE) inhibitors in this syndrome. To investigate these hypotheses, we examined expression of renin-angiotensin system compone nts in several tissues in a rodent model of post-myocardial infarction (MI) heart failure, and analysed whether such expression is modified by ACE inhibitor treatment. 2. Four groups of rats (n = 8-12 per group ) were studied 30 days after surgery: (A) sham-operated rats with no t reatment, (B) rats with post-MI heart failure induced by ligation of t he left coronary artery, (C) sham-operated rats treated with the ACE i nhibitor perindopril (1. mg day(-1) kg(-1)), and (D) rats as per B, bu t treated with perindopril. Expression of renin, angiotensinogen, ACE and angiotensin subtype 1 receptor was assessed by quantification of t heir respective mRNAs by Northern blotting. 3. Renal renin mRNA increa sed 2-fold in animals with MI (group B) compared with controls (group A) (P < 0.05) and between 50 and 100-fold after ACE inhibitor treatmen t (P < 0.001). No change in renin gene expression was found in any ext ra-renal site either following MI or after ACE inhibitor treatment. He patic angiotensinogen mRNA level was similar in all groups, but kidney angiotensinogen mRNA level was increased 1.6-fold (P < 0.01) in the g roups receiving perindopril. ACE mRNA level in the lung was not affect ed by ACE inhibitor treatment but decreased by 50% following MI (group s B and D, P < 0.01). This was associated with a similar (50%, P < 0.0 1) fall in lung ACE activity and was correlated with the severity of h eart failure. Angiotensin subtype 1 receptor mRNA level was not affect ed in any tissue by either MI or ACE inhibitor treatment. 4. We did no t find a systematic activation of tissue renin-angiotensin systems, as assessed by steady-state mRNA levels of key components of the system in experimental post-MI heart failure, or a major effect of ACE inhibi tor treatment on expression of these components. However, we observed tissue-specific changes in expression of selected components of the re nin-angiotensin system in the kidney and the lung in post-MI heart fai lure and after ACE inhibitor treatment, which may be of relevance to t he pathophysiology of the syndrome and the effects of ACE inhibition.