Key result
Pharmacological interruption of the renin-angiotensin system in animal models produces specific renal abnormalities, indicating AT1 receptor signaling is essential for normal renal development.
Intact signaling through AT1 receptors is a prerequisite for normal renal development, as demonstrated by severe renal abnormalities upon RAS blockade in animal models.
May warrant caution with RAS blockade in fetal/neonatal periods; leaves open human developmental relevance.
All components of the renin-angiotensin system (RAS) are highly expressed in the developing kidney in a pattern suggesting a role for angiotensin II in renal development. In support of this notion, pharmacological interruption of angiotensin II type-1 (AT(1)) receptor signalling 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 develop also in mice with targeted inactivation of genes encoding renin, angiotensinogen, angiotensin-converting enzyme, or both AT(1) receptor isoforms simultaneously. Taken together, these results clearly indicate that an intact signalling through AT(1) receptors is a prerequisite for normal renal development. The present report mainly reviews the renal abnormalities induced by blocking the RAS pharmacologically in experimental animal models. In addition, pathogenetic mechanisms are discussed.
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Chen et al. (2004) conducted a review in Renal development. Pharmacological interruption of angiotensin II type-1 (AT1) receptor signalling was evaluated on Renal abnormalities (papillary atrophy, abnormal wall thickening of intrarenal arterioles, tubular atrophy, impairment in urinary concentrating ability). Pharmacological interruption of the renin-angiotensin system in animal models produces specific renal abnormalities, indicating AT1 receptor signaling is essential for normal renal development.
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