Protection against ischemia: a physiological function of the renin-angiotensin system

The renin-angiotensin system (RAS) is involved in a complex mechanism that serves to presence the blood supply to organs so that they can maintain cel lular function. Angiotensin II exerts this effect, independently of the blo od pressure generated, through two time-related events: a fast opening of t he reserve collateral circulation and a much slower response of new vessel formation or angiogenesis. This effect is observed in rats with ligation of the abdominal aorta and in gerbils with abrupt or progressive unilateral c arotid artery ligation. Inhibition of the angiotensin-converting enzyme (AC E) or the angiotensin II receptor represses this effect, and it appears tha t it is mediated through a non-AT(1) receptor site of angiotensin II. Many tumors, both benign and malignant, express renin and angiotensin, It seems that the stimulating action of angiotensin II on angiogenesis could also be involved in preserving the blood supply to tumor cells. Administration of converting enzyme inhibitors increases survival and decreases tumor size in tumor-bearing rats. These observations support the hypothesis that the RAS , directly or indirectly, is involved in situations in which the restoratio n of blood supply is critical for the viability of cells and that it is pre sent not only in normal but also in pathological conditions such as tumors. In view of the ubiquitous presence of renins and angiotensins, it is also likely to be involved in other conditions, such as inflammation, arthritis, diabetic retinopathy, and retrolental fibroplasia, among others in which a ngiogenesis is prominent. Tn addition, angiotensin TI could be involved, th rough the counterbalance of the AT(1) and AT(2) receptors, in the rarefacti on of blood vessels as an etiologic component of essential hypertension. (C ) 2001 Elsevier Science Inc. All rights reserved.