Role of Myocardial Tissue Angiotensin (Ang) II in Cardiac Pathology

Summary

During the past couple of decades, the understanding of the tissue renin-angiotensin system (RAS) has increased especially in its role in compensatory hypertrophy and remodeling of the myocardium. Angiotensin (Ang) II-induced growth and proliferation of vascular smooth muscle cells are important elements in hypertension and atherosclerosis. Thus, treatment with angiotensin-converting enzyme (ACE) inhibitors has proved efficacious in preventing both atherosclerosis and hypertension. Left; ventricular remodeling following myocardial injury is another area of interest, where recent research has been focused. Increased contractile recovery in low-flow ischemia in hearts treated with ACE inhibitors was demonstrated recently in our laboratory. The contribution of RAS in other pathological conditions such as diabetes-induced cardiomyopathy has also been studied recently. These studies only provide preliminary results, and further studies are needed to completely delineate the role of myocardial RAS in disease-related cardiomyopathy. The development of ACE inhibitors of higher specific binding and high-lipid solubility has recently been the goal of many pharmaceutical companies, and many new ACE inhibitors have emerged in the market. Ang II receptor subtypes, AT₁ and AT₂, have also been the focus of recent research conducted by selective modulation of these receptors rather than by using ACE inhibitors to reduce Ang II levels. Future research in this area will provide tools to benefit from increased Ang II, yet will prevent the maladaptive deleterious effects of Ang II by antagonizing the specific subtype of receptor.