Pharmacological inhibition of the renin-angiotensin-aldosterone system reverses adverse myocardial structural remodelling and fibrosis in hypertensive heart disease.
The cardiac interstitium is composed of non-myocyte cells and a structural fibrillar protein network which plays a dominant role in governing the structure, architecture, and mechanical behaviour of the myocardium. Herein we review the fibrillar collagen network, its various components, and the functions they serve in the normal and structurally remodelled myocardium in arterial hypertension. The heterogeneity in myocardial structure, created by the altered behaviour of non-myocyte cells, particularly cardiac fibroblasts, which are responsible for collagen synthesis or degradation and thereby fibrous tissue accumulation, is a major determinant for the appearance of diastolic dysfunction and ultimately systolic myocardial failure. Regulatory mechanisms related to this fibrous tissue response are reviewed to draw attention to the hitherto neglected role of cardiac fibroblasts in mediating adverse structural remodelling of the myocardium and showing how this can be prevented through the use of pharmacological agents that interfere with the regulation of the myocardial collagen matrix. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodelling of the non-myocyte compartment. These include the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition and aldosterone receptor antagonism that were found to prevent myocardial fibrosis in the rat with renovascular hypertension. In the rat with genetic hypertension, established left ventricular hypertrophy and abnormal myocardial diastolic stiffness due to interstitial fibrosis, RAAS inhibition resulted in restoration of myocardial structure and function to normal. An overstimulated wound healing response that may occur with elevated arterial pressure, including the involvement of inflammatory cells, may be down-regulated by systemic or local RAAS inhibition and its interaction with the kinin-prostaglandin system. Thus, the cardioreparative effects of ACE inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease.
Brilla et al. (Wed,) conducted a review in arterial hypertension. RAAS inhibition was evaluated. Pharmacological inhibition of the renin-angiotensin-aldosterone system reverses adverse myocardial structural remodelling and fibrosis in hypertensive heart disease.