An intact renin-angiotensin system is a prerequisite for normal renal development.
All components of the renin-angiotensin system (RAS) are highly expressed in the developing kidney in a pattern that suggests a role for angiotensin II in renal development In support of this notion, pharmacological interruption of angiotensin II type-1 (AT1) receptor-mediated effects in animals with an ongoing nephrogenesis produces specific renal abnormalities characterized by papillary atrophy, abnormal wall thickening of intrarenal arterioles, tubular atrophy associated with expansion of the interstitium, and a marked 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 both AT1 receptor isoforms simultaneously. Taken together, these results clearly indicate that an intact signalling through AT1 receptors is a prerequisite for normal renal development In a recent study, an increased incidence of congenital anomalies of the kidney and urinary tract was detected in mice deficient in the angiotensin II type-2 receptor, suggesting that this receptor subtype is also involved in the development of the genitourinary tract The present report mainly reviews the renal abnormalities that have been induced by blocking the RAS pharmacologically or by gene targeting in experimental animal models. In addition, pathogenetic mechanisms and clinical implications are discussed.
Guron
G
G
Department of Physiology, Institute of Physiology and Pharmacology, Göteborg University, Sweden. gregor.guron@fysiologi.gu.se
Friberg
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D000818:Animals; D005260:Female; D018390:Gene Targeting; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000254:growth & development* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011247:Pregnancy; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin