Treatment of the cardiovascular remodeling in hypertensive patients

Abstract

The heart adapts to increasing afterload, 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 hallmark 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 stiffuess. 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 nonhemodynarnic factors in its pathogenesis (i.e. neurohumoral

activation, neurogenic stimuli, genetic predisposition, gender, age and race). An increase

in sympathetic (cd-adrenoceptors) and renin-angiotensin-aldosterone systerns (ATl 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 sorne antihypertensive drugs to produce regress cardiovascular remodelling (diuretics,

vasodilators, ~-blockers with intrinsic sympathomirnetic activity and dihydropyridines),

even through they reduce arterial blood presure to normotensive levels.

It is therefore, logical to suggest that a more ambitious approach to modem treatrnent

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.