RECIPROCAL REGULATION OF PULMONARY AND CARDIAC ANGIOTENSIN-CONVERTINGENZYME IN RATS WITH SEVERE LEFT-VENTRICULAR HYPERTROPHY

Objective: Numerous studies support the concept that cardiac angiotens in-converting enzyme (ACE) is involved in the pathophysiology of left ventricular hypertrophy. However, the pulmonary vasculature is conside red to be the most prominent site of ACE expression. We thus examined the tissue specificity of ACE regulation in rats with severe cardiac p ressure overload hypertrophy in transition to cardiac failure with sec ondary pulmonary hypertension. Methods and Results: Rats were studied 12 weeks after banding of the ascending aorta (LVH, n = 20) that resul ted in a 1.7-fold increase in left ventricular (LV) to body weight rat io. In addition, as compared to sham-operated rats (n = 20), we observ ed in LVH rats a 1.6-fold increase in right ventricular (RV) to body w eight ratio, the development of pulmonary hypertension, and elevated p lasma renin activities. Moreover, ACE mRNA and activity levels were mo n than 2-fold higher in both hypertrophied ventricles (P < 0.01, each) . In contrast, pulmonary ACE mRNA and activity levels were markedly de creased in animals with LVH (more than 30%, respectively, P < 0.05 vs, sham). Interestingly, LV and RV ACE activity, as well as systolic pul monary artery pressure and plasma renin activity, were all inversely r elated to pulmonary ACE activity. In order to differentiate the potent ial role of elevated renin in the down-regulation of pulmonary ACE, ad ditional rats (n = 12) were treated with furosemide that resulted in a 8-fold rise in plasma renin activity, but only in a marginal decrease of pulmonary ACE mRNA levels and activity (-10% vs. sham (n = 8), P-v alue n.s.). Conclusions: The data indicate tissue specific reciprocal regulation of pulmonary and cardiac ACE in rats with cardiac pressure overload hypertrophy and pulmonary hypertension, a phenomenon that may potentially result in a partial shift of angiotensin II formation fro m the pulmonary to the cardiac circulation. (C) 1998 Elsevier Science B.V.