Growth or antigrowth: angiotensin and the endothelium

Antihypertensive drugs that interfere with the renin-angiotensin system, such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, are increasingly being perceived to exert effects beyond blood pressure control, for instance on vascular structure and function. In a recent study we demonstrated that early-onset treatment of spontaneously hypertensive rats with an ACE inhibitor induced an increase in myocardial capillary length density independently of the antihypertensive and antihypertrophic actions of the drug. The aim of the present work was to focus on the growth-modulating effects of angiotensin II on vascular cells and the differential role played by the two angiotensin II receptor subtypes, AT1 and AT2, in the regulation of cell growth and differentiation.

Recent findings indicate that angiotensin II exerts different growth-modulating actions depending on the presence or absence of angiotensin II receptor subtypes on a given cell. The growth-promoting effect of angiotensin II is mediated by the AT1 receptor and is associated with the increased expression of growth factors and immediate early genes. In endothelial cells, this effect is counteracted by the antiproliferative actions of the AT2 receptor. Angiotensin II may also be involved in the process of angiogenesis and development mediated by AT1 and AT2 receptors expressed in various tissues.