The renin-angiotensin-aldosterone system: A specific target for hypertension management

Angiotensin II plays a central role in the regulation of systemic arterial pressure through its systemic synthesis via the renin-angiotensin-aldostero ne cascade. It acts directly on vascular smooth muscle as a potent vasocons trictor, In addition,it affects cardiac contractility and heart rate throug h its action on the sympathetic nervous system. Angiotensin II also alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldoster one. Furthermore, it enhances thirst and stimulates the secretion of the an tidiuretic hormone. Consequently, angiotensin II plays a critical role in b oth the acute and chronic regulation of blood pressure through its systemic endocrine regulation. A potent neurohormone that regulates systemic arterial pressure, angiotensi n II also affects vascular structure and function via paracrine and autocri ne effects of local tissue-based synthesis. This alternate pathway of angio tensin II production is catalyzed in tissues via enzymes such as cathepsin G, chymostatin-sensitive angiotensin II-generating enzyme, and chymase. Int ratissue formation of angiotensin II plays a critical role in cardiovascula r remodeling. Upregulation of these alternate pathways may occur through st retch, stress, and turbulence within the blood vessel. Similar processes wi thin the myocardium and glomeruli of the kidney may also lead to restructur ing in these target organs, with consequent organ dysfunction. Additionally , angiotensin II may increase receptor density and sensitivity for other fa ctors that modulate growth of vascular smooth muscle, such as fibroblast gr owth factor, transforming growth factor beta-1, platelet-derived growth fac tor, and insulin-like growth factors. Atherosclerosis may also be related, in part, to excessive angiotensin II effect on the vessel wall, which cause s smooth muscle cell growth and migration. It also activates macrophages an d increases platelet aggregation. Angiotensin II stimulates plasminogen act ivator inhibitor 1 and directly causes endothelial dysfunction. Other postu lated effects of angiotensin II on vascular structure that could promote at herogenesis include inhibition of apoptosis, increase in oxidative stress, promotion of leukocyte adhesion and migration, and stimulation of thrombosi s. Inhibition of angiotensin II synthesis with an angiotensin-converting enzym e inhibitor has been demonstrated to be beneficial in-modifying human disea se progression. This is clearly apparent in clinical trials involving patie nts with diabetic nephropathy, postmyocardial infarction, or advanced degre es of systolic heart failure. Thus, angiotensin II is an excellent target f or pharmacologic blockade. Not only does it play a pivotal role in both the acute and chronic regulation of systemic arterial pressure, but it also is an important modulator of cardiovascular structure and function and may be specifically involved in disease progression. Modification of angiotensin II effect may therefore serve a dual purpose. Not only will blood pressure reduction occur with less stretch, stress, and turbulence of the vascular w all, but there will also be less stimulation, either directly or indirectly , for restructuring and remodeling of the cardiovascular tree. Am J Hyperte ns 1999;12:205S-213S (C) 1999 American Journal of Hypertension, Ltd.