Reciprocal regulation of pulmonary and cardiac angiotensin-converting enzyme in rats with severe left ventricular hypertrophy.
OBJECTIVE
Numerous studies support the concept that cardiac angiotensin-converting enzyme (ACE) is involved in the pathophysiology of left ventricular hypertrophy. However, the pulmonary vasculature is considered to be the most prominent site of ACE expression. We thus examined the tissue specificity of ACE regulation in rats with severe cardiac pressure overload hypertrophy in transition to cardiac failure with secondary pulmonary hypertension.


RESULTS
Rats were studied 12 weeks after banding of the ascending aorta (LVH, n = 20) that resulted in a 1.7-fold increase in left ventricular (LV) to body weight ratio. In addition, as compared to sham-operated rats (n = 20), we observed in LVH rats a 1.6-fold increase in right ventricular (RV) to body weight ratio, the development of pulmonary hypertension, and elevated plasma renin activities. Moreover, ACE mRNA and activity levels were more than 2-fold higher in both hypertrophied ventricles (P < 0.01, each). In contrast, pulmonary ACE mRNA and activity levels were markedly decreased in animals with LVH (more than 30%, respectively, P < 0.05 vs. sham), Interestingly, LV and RV ACE activity, as well as systolic pulmonary artery pressure and plasma renin activity, were all inversely related to pulmonary ACE activity. In order to differentiate the potential role of elevated renin in the down-regulation of pulmonary ACE, additional 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-value 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 from the pulmonary to the cardiac circulation.
Pfeifer
M
M
Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität, Regensburg, Germany.
Bruckschlegel
G
G
Holmer
S R
SR
Paul
M
M
Riegger
A J
AJ
Schunkert
H
H
D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000097:blood / Q000201:enzymology; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000201:enzymology*; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011669:Pulmonary Wedge Pressure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood
D004232:Diuretics; D012333:RNA, Messenger; D005665:Furosemide; D007703:Peptidyl-Dipeptidase A; D012083:Renin