RELATIONSHIP BETWEEN STRUCTURE AND FUNCTI ON IN HYPERTENSIVE HEART-DISEASE

Based on the epidemiologic data of the Framingham heart study, arteria l hypertension and coronary artery disease are the most frequent etiol ogic factors for the development of heart failure. In the pressure ove rloaded heart, hypertrophic growth of the myocardium includes the enla rgement of cardiac myocytes stimulated by ventricular loading. Non-myo cyte cell growth involving cardiac fibroblasts may also occur but is n ot primarily regulated by the hemodynamic load. Cardiac fibroblast act ivation is responsible for the accumulation of fibrillar type I and ty pe III collagens within the interstitium while vascular smooth muscle cell growth accounts for the medial thickening of resistence vessels. This remodeling of the cardiac interstitium represents a major determi nant of pathological hypertrophy in that it accounts for abnormal myoc ardial stiffness and impaired coronary vasodilator reserve. leading to ventricular diastolic and systolic dysfunction and ultimately to the appearance of symptomatic heart failure. Several lines of evidence sug gest that the renin-angiotensin-aldosterone system is involved in regu lating the structural remodeling of the nonmyocyte compartment, includ ing the cardioprotective effects of angiotensin converting enzyme (ACE ) inhibition that was found to prevent myocardial fibrosis in the rat with renovascular hypertension. In rats with genetic hypertension, est ablished left ventricular hypertrophy, abnormal diastolic stiffness du e to interstitial fibrosis, and reduced coronary vasodilator reserve a ssociated with medial wall thickening of intramyocardial resistance ve ssels, the ACE inhibitor lisinopril was able to restore myocardial str ucture and function to normal. These cardioreparative properties of AC E inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease.