Glomerular eNOS gene expression during postnatal maturation and AT1 receptor inhibition

Ratliff, Brian B.; Rodebaugh, Justin; Sekulic, Miroslav; Solhaug, Michael J.

doi:10.1007/s00467-007-0489-z

Cited by 9 publications

(3 citation statements)

References 29 publications

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“…Solhaug et al demonstrated pre-perfusion of an AT1 receptor inhibitor prior to NOS inhibition with L-NAME renal perfusion blunted the effects of L-NAME in the newborn, but not the adult, kidney (11). Ratliff et al demonstrated AT1 receptor inhibition in the newborn piglet attenuated glomerular eNOS expression (27). However, information on NOS regulation is much more available in the adult.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Regulates NOS Expression in Afferent Arterioles of the Developing Porcine Kidney

et al. 2010

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NO protection is crucial against angiotensin II (ANG II) mediated vasoconstriction in postnatal preglomerular resistance vessels. Although whole kidney NOS is developmentally regulated, NOS regulation in developing renal resistance vessels is unknown. The hypothesis was NOS expression and function in developing afferent arterioles are regulated by ANG II through AT1 and AT2 receptors. Afferent arterioles from porcine kidneys, ages newborn, 7, 21 d, and adult, were dissected using a polybead perfusion technique. Dissected afferent arterioles were treated with ANG II and with either the AT1 receptor inhibitor candesartan or the AT2 receptor inhibitor PD 123319 and evaluated for NOS isoform expression and NOS enzymatic activity. Although NOS activity and neuronal NOS (nNOS) expression were greater in the newborn than in the adult, endothelial NOS (eNOS) expression was greater in the adult. ANG II increased NOS activity and eNOS expression at all ages, but nNOS expression only in developing afferents. AT1 and AT2 receptor blockade significantly attenuated NOS activity and eNOS expression at all ages, but nNOS expression only in developing afferents. ANG II regulates nNOS and eNOS expression and NOS activity in afferent arterioles of the developing kidney via AT1 and AT2 receptors.

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Section: Discussionmentioning

confidence: 99%

Angiotensin II Regulates NOS Expression in Afferent Arterioles of the Developing Porcine Kidney

et al. 2010

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“…The appropriate maturation of the other constituent cellular elements of the glomerulus has been shown to rely upon the effect of inductive signals such as platelet-derived and vascular endothelial-derived growth factors (PDGF and VEGF) derived from podocytes [27]. An inability of Ros to correct deficits in these pathways could also have a role to play in the incomplete protection of glomerular development during neonatal UUO.…”

Section: Discussionmentioning

confidence: 99%

Rosuvastatin Preserves Renal Structure following Unilateral Ureteric Obstruction in the Neonatal Rat

Mazzei

García²,

Altamirano³

et al. 2011

Am J Nephrol

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Background/Aims: Unilateral ureteric obstruction (UUO) in neonatal rodents can be used as a paradigm for in utero obstruction in humans and a platform for studying the potential of novel therapies for congenital obstructive nephropathy. The present study examined the effect of rosuvastatin (Ros) on key morphometric measures of renal injury and corresponding gene expression correlates following neonatal UUO in the rat. Methods: Neonatal rats subjected to UUO and controls were treated daily with vehicle or Ros for 14 days. Quantification of tubular dilatation, glomerular size and number and tubulointerstitial fibrotic area was performed and changes validated by reference to appropriate renal gene expression correlates. Results: UUO increased tubular diameter and interstitial fibrosis by 2.7- and 7-fold, respectively, in parallel with increases in renal transforming growth factor-β₁ (TGF-β₁) and tumor necrosis factor-α (TNF-α) mRNA levels. Glomerular number and size were reduced by 52 and 33%, respectively. Reductions in WT-1 mRNA and protein expression were noted following obstruction occurring in tandem with reduced mRNA levels for BMP-7 and E-cadherin. Ros attenuated tubular dilatation (33%) and interstitial fibrosis (72%) in association with the normalization of renal TGF-β₁ and TNF-α mRNA levels. Ros improved glomerular number and size (30 and 50%), and preserved mRNA and protein expression levels of WT-1 and normalized mRNA levels for BMP-7 and E-cadherin. Conclusions: Ros treatment attenuated all changes, most notably the increase in interstitial fibrosis. Notably, Ros treatment was unable to completely salvage glomerular development. Together these data highlight the therapeutic potential and limitations of Ros in neonatal obstruction.

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“…Importantly, studies in animal models with ongoing postnatal nephrogenesis have shown that after birth there initially remains a low blood flow to the outer renal cortex which is likely a protective mechanism to protect developing, immature glomeruli in this region of the kidney [72]. It is unknown, however, whether this protective pattern of blood distribution is also present in the kidney of the preterm human neonate, which is especially important given that these kidneys are structurally very immature and nephrogenesis is still ongoing in the outer renal cortex after birth.…”

Section: Renal Blood Flow Increases At Birthmentioning

confidence: 99%

Low Birth Weight due to Intrauterine Growth Restriction and/or Preterm Birth: Effects on Nephron Number and Long-Term Renal Health

Zohdi

Sutherland

Lim

et al. 2012

International Journal of Nephrology

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Epidemiological studies have clearly demonstrated a strong association between low birth weight and long-term renal disease. A potential mediator of this long-term risk is a reduction in nephron endowment in the low birth weight infant at the beginning of life. Importantly, nephrons are only formed early in life; during normal gestation, nephrogenesis is complete by about 32–36 weeks, with no new nephrons formed after this time during the lifetime of the individual. Hence, given that a loss of a critical number of nephrons is the hallmark of renal disease, an increased severity and acceleration of renal disease is likely when the number of nephrons is already reduced prior to disease onset. Low birth weight can result from intrauterine growth restriction (IUGR) or preterm birth; a high proportion of babies born prematurely also exhibit IUGR. In this paper, we describe how IUGR and preterm birth adversely impact on nephrogenesis and how a subsequent reduced nephron endowment at the beginning of life may lead to long-term risk of renal disease, but not necessarily hypertension.

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Glomerular eNOS gene expression during postnatal maturation and AT1 receptor inhibition

Cited by 9 publications

References 29 publications

Angiotensin II Regulates NOS Expression in Afferent Arterioles of the Developing Porcine Kidney

Angiotensin II Regulates NOS Expression in Afferent Arterioles of the Developing Porcine Kidney

Rosuvastatin Preserves Renal Structure following Unilateral Ureteric Obstruction in the Neonatal Rat

Low Birth Weight due to Intrauterine Growth Restriction and/or Preterm Birth: Effects on Nephron Number and Long-Term Renal Health

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