An intact renin-angiotensin system is a prerequisite for normal renal development

All components of the renin-angiotensin system (RAS) are highly expressed i n the developing kidney in a pattern that suggests a role for angiotensin I I in renal development. In support of this notion, pharmacological interrup tion of angiotensin II type-1 (AT(1)) receptor-mediated effects in animals with an ongoing nephrogenesis produces specific renal abnormalities charact erized by papillary atrophy, abnormal wall thickening of intrarenal arterio les, tubular atrophy associated with expansion of the interstitium, and a m arked impairment in urinary concentrating ability. Similar changes in renal morphology and function also develop in mice with targeted inactivation of the genes that encode angiotensinogen, angiotensin converting enzyme, or b oth AT(1) receptor isoforms simultaneously. Taken together, these results c learly indicate that an intact signalling through AT(1) receptors is a prer equisite for normal renal development. In a recent study, an increased inci dence of congenital anomalies of the kidney and urinary tract was detected in mice deficient in the angiotensin II type-2 receptor, suggesting that th is receptor subtype is also involved in the development of the genitourinar y tract. The present report mainly reviews the renal abnormalities that hav e been induced by blocking the RAS pharmacologically or by gene targeting i n experimental animal models. In addition, pathogenetic mechanisms and clin ical implications are discussed. J Hypertens 2000, 18:123-137 (C) Lippincot t Williams & Wilkins.