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 preserve the blood supply to organs so that they can maintain cellular function. Angiotensin II exerts this effect, independently of the blood pressure generated, through two time-related events: a fast opening of the 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 carotid artery ligation. Inhibition of the angiotensin-converting enzyme (ACE) or the angiotensin II receptor represses this effect, and it appears that it is mediated through a non-AT1 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 restoration of blood supply is critical for the viability of cells and that it is present 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 angiogenesis is prominent. In addition, angiotensin II could be involved, through the counterbalance of the AT1 and AT2 receptors, in the rarefaction of blood vessels as an etiologic component of essential hypertension.
Achard
J
J
Department of Physiology, Centre Hospitalier Universitaire Dupuytren, Limoges, France.
Fournier
A
A
Mazouz
H
H
Caride
V J
VJ
Penar
P L
PL
Fernandez
L A
LA
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D007511:Ischemia / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D020011:Protective Agents / Q000378:metabolism / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000502:physiology*
D043925:Angiogenesis Inducing Agents; D020011:Protective Agents; D000804:Angiotensin II