MAPK and angiotensin II receptor in kidney of newborn rats from losartan-treated dams

et al. 2009

Braz J Med Biol Res

Experimental and clinical evidence suggests that angiotensin II (AII) participates in renal development. Renal AII content is several-fold higher in newborn rats and mice than in adult animals. AII receptors are also expressed in higher amounts in the kidneys of newborn rats. The kidneys of fetuses whose mother received a type 1 AII receptor (AT 1 ) antagonist during gestation present several morphological alterations. Mutations in genes that encode components of the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Morphological changes were detected in the kidneys of 3-weekold angiotensin-deficient mice. Mitogen-activated protein kinases (MAPKs) are important mediators that transduce extracellular stimuli to intracellular responses. The MAPK family comprises three major subgroups, namely extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinases (JNK), and p38 MAPK (p38). Important events in renal growth during nephrogenesis such as cellular proliferation and differentiation accompanied by apoptosis on a large scale can be mediated by MAPK pathways. A decrease in glomerulus number was observed in embryos cultured for 48 and 120 h with ERK or p38 inhibitors. Many effects of AII are mediated by MAPK pathways. Treatment with losartan during lactation provoked changes in renal function and structure associated with alterations in AT 1 and type 2 AII (AT 2 ) receptors and p-JNK and p-p38 expression in the kidney. Several studies have shown that AII and MAPKs play an important role in renal development. However, the relationship between the effects of AII and MAPK activation on renal development is still unclear.

Section: Renal Development In Offspring Of Mothers That Received Angimentioning

confidence: 73%

Roles of mitogen-activated protein kinases and angiotensin II in renal development

Balbi

Francescato

et al. 2009

Braz J Med Biol Res

“…The MAPK pathways can be activated by oxidative stress, leading to the inflammation processes, 58 apoptosis and the development of renal lesions in losartan-treated pups. 3 However, the effect of tempol treatment in these animals was limited probably because AII also has several effects that are not mediated by oxidative stress such as the proliferation and differentiation of the tubular, interstitial and vascular cells. 4,5,14,15 It can explain the abnormalities in renal vasculature and tubule interstitial compartment observed in both groups of losartan-treated rats, considering that cell proliferation and differentiation are important events in development.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Clinical and experimental evidence indicates that the renin-angiotensin system (RAS) participates in renal development. [3][4][5][6] All RAS components are expressed early at a high intensity in embryogenesis. 7,8 Angiotensin II (AII) stimulates cultured mesangial cells to produce various extracellular matrix (ECM) components 9 and promotes cell proliferation and differentiation.…”

Section: Introductionmentioning

confidence: 99%

The role of oxidative stress in renal injury induced in rats by losartan exposure during lactation

J Renin Angiotensin Aldosterone Syst

Francescato

Costa

et al. 2013

Self Cite

Introduction: Rats exposed to angiotensin II (AII) receptor antagonists during lactation present progressive disturbances in renal development that lead to progressive alterations in renal function and structure. This study evaluates the role of oxidative stress in the renal changes induced by exposure to losartan, a type 1 AII receptor antagonist, in rats during lactation. Materials and methods: Male Wistar pups were divided into: Control, pups of dams that received 2% sucrose solution; Control-tempol, pups of dams that received tempol (0.34 g/l), a superoxide dismutase mimetic compound; Losartan, pups of dams that received losartan (100 mg/kg/day), and Losartan-tempol, pups of dams that received losartan and tempol. Losartan and/or tempol were administered during lactation. Blood and urine samples were collected at 21 or 60 days, and the kidneys were removed. Results: Losartan-treated pups exhibited disturbances in renal function and structure that persisted into adulthood. Tempol treatment reduced oxidative stress and attenuated the changes induced by losartan in the glomerular filtration rate, desmin expression at the glomerular edge, vimentin in tubular cells, as well as apoptosis and inflammatory infiltration in the renal cortex. Conclusion: Oxidative stress contributes at least in part to the renal injury observed in pups exposed to losartan during lactation.

“…Clinical and experimental evidence indicates that the renin-angiotensin system participates in renal development [1,2,3,4,5,6,7,8,9,10,11,12]. All components of the renin-angiotensin system are highly expressed early in embryogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Inhibition of the renin-angiotensin system by administration of angiotensin II antagonists in rats during postnatal development causes abnormalities in renal structure characterized by reduced glomerular volume, tubular dilation, papillary atrophy and interstitial expansion of the renal cortex [1,12,13,14] that lead to a progressive loss of renal function [12]. It was proposed that the structural abnormalities in this experimental model might result in part from developmental disruption of the vascular and tubular compartment of the kidney [14].…”

Section: Introductionmentioning

confidence: 99%

Postnatal Renal Abnormalities in Rats Exposed to Losartan during Lactation

Francescato²,

Silva³

et al. 2011

Nephron Exp Nephrol

Self Cite

Background/Aims: Rats exposed to losartan during lactation exhibit progressive changes in renal function and structure. This study analyzed the early events in pups from dams that received losartan during lactation. Methods: Male Wistar rats from dams that received 2% sucrose (control, n = 25) or losartan (100 mg/kg/day) diluted in 2% sucrose (n = 33) during lactation were anesthetized 21 days after birth. Blood and urine samples were collected to assess renal function, and kidneys were removed for histological, immunohistochemical, Western blot, lipid peroxidation and glutathione analyses. Results: The group exposed to losartan exhibited increased albuminuria and fractional sodium and potassium excretion, decreased glomerular area and interstitial expansion. Immunohistochemical analyses demonstrated increased tubulointerstitial macrophage infiltration, apoptosis and increased vimentin and α-smooth-muscle-actin expression in animals exposed to losartan. In addition, the glomeruli of animals exposed to losartan exhibited increased peripheral desmin expression and reduced glomerular epithelial protein 1 and podocin expression compared to controls. Lastly, renal lipid peroxidation and glutathione levels were higher in the losartan-treated pups. Conclusion: Pups exposed to losartan during lactation exhibited adverse changes in renal function and structure, and tubulointerstitial inflammation at 21 days of age that were associated with apoptosis and oxidative stress.