Relation of renin-angiotensin system activity to left ventricular hypertrophy and function in experimental and human hypertension.

This article examines available data concerning the hypothesis that the renin-angiotensin system directly stimulates cardiac hypertrophy and dysfunction in hypertension. Several experiments support a direct effect of angiotensin on myocardial protein synthesis and suggest that this may be independent of adrenergic influences. However, the role played by the renin system in the pathogenesis of hypertensive cardiac hypertrophy may be small, for left ventricular (LV) muscle mass is not systematically greater in high-renin as opposed to low-renin forms of experimental or human hypertension. In animal studies, regression of LV hypertrophy is more consistently observed in response to drugs that inhibit as opposed to those that stimulate renin-angiotensin system activity (i.e., converting enzyme inhibitors or beta-adrenoceptor blockers vs. diuretics or direct vasodilators), although the difference is more quantitative than absolute. Similarly, significant reductions in LV mass occurred in 13 of 16 human trials with converting enzyme inhibitors or beta blockers as opposed to 2 of 10 trials with diuretics or vasodilators (mean = 7.11; p less than 0.01). However, uncertainties regarding the degree of reduction in angiotensin II and adrenergic effects, possible interactions between these systems, and incomplete characterization of induced changes in hemodynamic load on the heart all limit the interpretation of available studies. Preliminary data suggest that an inverse relation exists between renin-angiotensin system activity and LV systolic performance in primary and secondary human hypertension, a possibility that merits further study.