Angiotensin II regulates nephrogenesis and renal vascular development

Abstract

To test the hypothesis that angiotensin II (ANG II) is necessary for normal embryonic and postnatal kidney development, the effect of angiotensin receptor blockade or angiotensin converting enzyme inhibition on nephrovascular development was studied in newborn Sprague-Dawley rats and in Rana catesbeiana tadpoles undergoing prometamorphosis. Blockade of ANG II type 1 receptor (AT1) in newborn rats induced an arrest in nephrovascular maturation and renal growth, resulting in altered kidney architecture, characterized by fewer, thicker, and shorter afferent arterioles, reduced glomerular size and number, and tubular dilatation. Inhibition of ANG II generation in tadpoles induced even more marked developmental renal abnormalities. Blockade of ANG II type 2 receptor (AT2) in newborn rats did not alter renal growth or morphology. Results indicate that ANG II regulates nephrovascular development, a role that is conserved across species.

Development of the Renal Arterioles

“…Interestingly, inhibition of angiotensin generation in rana catesbiana tadpoles undergoing prometamorphosis results in even more marked renal abnormalities with persistence of pronephric tubes and areas of undifferentiated mesenchyme. 49 These experiments, as well as those of other investigators, indicate that not only is angiotensin II necessary for nephrovascular development but also its vascular growth actions are conserved across the phylogenetic scale. 49 In agreement with those findings, deletion of any of the genes of the renin-angiotensin system (angiotensin-converting enzyme, renin, angiotensinogen, and AT1AϩB) results in similar abnormalities ( Figure 6).…”

“…49 These experiments, as well as those of other investigators, indicate that not only is angiotensin II necessary for nephrovascular development but also its vascular growth actions are conserved across the phylogenetic scale. 49 In agreement with those findings, deletion of any of the genes of the renin-angiotensin system (angiotensin-converting enzyme, renin, angiotensinogen, and AT1AϩB) results in similar abnormalities ( Figure 6). The growth effects of angiotensin II are not limited to the renal arterioles and extend to the postglomerular circulation.…”

Prenatal Programming of Hypertension

“…The role of the RAS in altered renal development has received considerable attention. Angiotensin II is known to be important in normal renal development (109,110), and variations in dietary protein can alter the RAS (111). In the rat low-protein model, we have shown that renal tissue renin protein and mRNA, AT1R protein and mRNA, and angiotensin II levels are reduced in the newborn and young offspring compared with controls (16,19,97).…”

What Have We Learned from Gene Targeting Studies for the Renin Angiotensin System of the Kidney?

“…Administration of ACEinhibitors in hypertensive women during pregnancy results in severe malformations in the fetus, including kidney anomalies (48,49). Similar histological changes were also found in several animal models using pharmacological Ang II inhibitors (50,51). Moreover, the ACE inhibitor suppresses glomerular growth in maturing rats (52).…”