Time course sequences of angiotensin converting enzyme and chymase-like activities during development of right ventricular hypertrophy induced by pulmonary artery constriction in dogs.

ACE and chymase play crucial roles in the establishment of pressure overload-induced cardiac hypertrophy. In the present study, time sequences of ACE and chymase-like activities, and their correlation with hypertrophic changes including free wall thickness and cardiac fibrosis, were elucidated in dogs with constant pressure overload to the right ventricle. Pulmonary artery banding (PAB) was applied so that the diameter of the main pulmonary artery was reduced to 60% of the original size, right ventricular pressure was elevated by about 70%, and pulmonary artery flow was increased by about three times of that in sham operation groups. These increases remained unchanged 15, 60, and 180 days after PAB, suggesting that constant right ventricular pressure overload was obtained, at least during this period. The diameter of the right ventricular myocyte was slightly increased and the percentage of fractional shortening was decreased 15 days after PAB. Right ventricular wall thickness and interstitial collagenous fiber were, however, not different from those of sham-operated dogs, suggesting that this period is a period of adaptation to the overload. Sixty days after PAB, the diameter of the right ventricular myocyte was further increased, and right ventricular wall thickness and interstitial collagenous fiber were also increased. These changes were almost identical even 180 days after PAB. Thus, stable hypertrophy was elicited from 60 through 180 days after PAB. ACE activity was facilitated at the adaptation period to the overload (15 days after PAB), but chymase activity was not facilitated at this period. On the other hand, both ACE and chymase-like activities were unchanged in the earlier phase (60 days after PAB) of stable hypertrophy, but facilitated in the latter phase (180 days after PAB). These findings suggest the pathophysiologic roles of these enzymes may be different over the time course of pressure overload-induced hypertrophy. Copyright 2004 Elsevier Inc.