Treatment of the cardiovascular remodeling in hypertensive patients
Tamargo, J.
Ars Pharm.36;(4);527-546, (1995)
Key words: Arterial hypertension, Left ventricular hypertrophy, Vascular remodelling, Drug therapyAbstract
The heart adapts to increasing after load, such as that which occurs in arterial hypertension with an increase in wall thickness (left ventricular hipertrophy) in order to bring wall stress back to normal. Adult cardiac myocytes are unable to proliferate, so that myocyte hypertrophy is the hall mark of left ventricular hipertrophy. Cardiac remodelling, however, involves not only myocyte growth but also hypertrophy/hyperplasia of nonmyocyte cells within the myocardium. The result is a perivascular and intersticial fibrosis that impair myocardial stiffness. In response to increased arterial pressure, the vessel structure is altered such that the ratio of the width of the wall to the width of the lumen is increased by either an increase in mass or rearrangements of vascular smooth muscle cells and other cellular and noncellular elements of the vascular wall. These changes increased vascular reactivity, potentiated the increase in peripheral vascular resistance characteristic of hypertension and attenuated the coronary reserve to ischemic provocation. The poor correlation between blood pressure and the magnitude of cardiovascular remodelling strongly suggests a role for nonhemodynamic factors in its pathogenesis (i.e. neurohumoral activation, neurogenic stimuli, genetic predisposition, gender, age and race). An increase in sympathetic (alfa-1-adrenoceptors) and renin-angiotensin-aldosterone systems (AT1 receptors) piay an important role in both cardiac myocyte and nonmyocyte growth and remodelling. Experimental and clinical studies have demonstrated that all antihypertensive agents may prevent or cause regression of cardiovascular remodelling. However, despite their equipotent blood - lowering effects, there are not only marked differences in the ability of different types of antihypertensive drugs to prevent or reverse cardiovascular remodelling but also whithin the same class of pharmacological drugs. Antihypertensive drugs that modulate the sympathetic or renin-angiotensin-aldosterone systems or the intracellular free Ca concentration can reverse cardiovascular remodelling, this effect being more pronounced with ACE inhibitors. Reflex neurohumoral activation may be responsible for the failure of some antihypertensive drugs to produce regress cardiovascular remodelling (diuretics, vasodilators, beta-blockers with intrinsic sympathomimetic activity and dihydropyperidines), even through they reduce arterial blood presure to normotensive levels.
It is therefore, logical to suggest that a more ambitious approach to modern treatment of hypertension would not only be to reduce elevated blood pressure, but also to introduce an important additional goal, namely to attain regression of structurally remodelled heart and vasculture to, or toward, normal structure and function. Only this therapeutic approach might truly reduce the risk of cardiovascular complications in the hipertensive patient.
Return to index