The cardiac structure-function relationship and the renin-angiotensin-aldosterone system in hypertension and heart failure.
According to the Framingham Study, arterial hypertension and coronary artery disease are the major etiologic factors in the development of heart failure. Regulatory systems that may affect heart failure include the Frank-Starling mechanism, neurohormonal responses, cardiac growth and peripheral oxygen delivery. Recently, the interrelationship between the neuroendocrine system and cardiac growth has aroused much interest. In the pressure- or volume-overloaded heart, hypertrophic growth of the myocardium includes the enlargement of cardiac myocytes, an adaptation governed by ventricular loading. Nonmyocyte cell growth involving cardiac fibroblasts may also occur but is not primarily regulated by the hemodynamic load. Cardiac fibroblast activation is responsible for the accumulation of fibrillar type I and type III collagens within the interstitium and adventitia of intramyocardial coronary arteries, while vascular smooth muscle cell growth accounts for the medial thickening of these vessels. This remodeling of the cardiac interstitium is a major determinant of pathological hypertrophy in that it accounts for abnormal myocardial stiffness and impaired coronary vasodilator reserve, leading to ventricular diastolic and systolic dysfunction and, ultimately, symptomatic heart failure. Several lines of evidence suggest that the renin-angiotensin-aldosterone system is involved in regulating the structural remodeling of the nonmyocyte compartment; this accounts for the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition, which prevents myocardial fibrosis in rats with renovascular hypertension. In rats with genetic hypertension, established left ventricular hypertrophy, abnormal diastolic stiffness due to interstitial fibrosis and reduced coronary vasodilator reserve associated with medial wall thickening of intramyocardial resistance vessels, the ACE inhibitor lisinopril restored myocardial structure and function towards normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Brilla
C G
CG
Philipps University of Marburg, Germany.
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D002478:Cells, Cultured / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen