Objective: This study was undertaken to determine the biochemical and left ventricular functional changes associated with reversal of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR).
Design: Male SHR and normotensive Wistar-Kyoto (WKY) rats, aged 19 weeks, were treated for 3 weeks with vehicle, amlodipine (10 mg/kg), benazepril (10 mg/kg) or the combination of both agents (4 mg/kg amlodipine and 4 mg/kg benazepril). Left ventricular function was assessed while blood was infused rapidly, at pharmacologically reduced and pretreatment mean arterial pressure (MAP).
Results: All treatments reduced MAP and left ventricular mass significantly in SHR. Myocardial protein, RNA and myocardial collagen content were reduced proportionately in all treatment groups in SHR, but not in WKY rats. DNA remained unchanged in all groups. Increased right ventricular mass was produced by amlodipine in both SHR and WKY rats (SHR +11.3%; WKY +9.8%), but this was prevented by cotreatment with benazepril. Right ventricular protein and collagen increased significantly with amlodipine in SHR but not WKY rats, and there were no changes in right ventricular RNA and DNA contents in either strain. Amlodipine improved, benazepril impaired and the combination of both agents maintained left ventricular pumping ability when pressure was increased abruptly to pretreatment levels in WKY rats. In contrast, when afterload was increased abruptly in SHR to pretreatment levels, neither amlodipine nor benazepril affected pumping ability, although it was enhanced by the combination.
Conclusions: These data demonstrate that amlodipine, benazepril and their combination reduced left ventricular mass in SHR. This reversal of LVH was associated with proportional reductions in mycotic protein, RNA and collagen, but not DNA. Therefore, it seems unlikely that LVH reversal with these agents was associated with increased fibrous tissue or impaired left ventricular performance. Finally, addition of the angiotensin converting enzyme inhibitor prevents the increase in right ventricular mass produced by the calcium antagonist.