Postnatal Renal Abnormalities in Rats Exposed to Losartan during Lactation

Marin, Evelyn Cristina Santana; Francescato, Heloı́sa Della Coletta; Silva, Cleonice Giovanini Alves da; Costa, R. S.; Coimbra, Terezila Machado

doi:10.1159/000328337

Cited by 6 publications

(11 citation statements)

References 71 publications

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“…We also observed an increase in FE + Na in rats that received losartan during renal development, which indicated that renal sodium transport was altered. The changes in glomerular filtration rate observed in the present study were similar to those observed in other studies that used this model (5,7,20,21).…”

Section: Discussionsupporting

confidence: 91%

“…The renin-angiotensin system (RAS) plays an important role in expansion, migration, and formation of renal structure during nephrogenesis (4). Results from our studies and others have shown that pharmacological RAS inhibition or genetic deletion of downstream signaling components of RAS (1,3,(5)(6)(7)(8) result in impaired development of glomeruli and preglomerular vasculature. Angiotensin II (ANGII) also affects the post-glomerular circulation.…”

Section: Introductionmentioning

confidence: 75%

“…Calcitriol treatment attenuated these effects, likely through promotion of cell proliferation and differentiation. We previously showed that animals at 21 days postnatal exposed to losartan during lactation showed abnormalities in renal function, structure, hydronephrosis, and increased expression of mesenchymal markers (7,20). Mecawi et al (25) also observed hydronephrosis in animals exposed to captopril, an ACE (angiotensin-converting enzyme) inhibitor, characterized by distension and dilation of the renal pelvis.…”

Section: Discussionmentioning

confidence: 99%

“…Morphometric changes have been previously evaluated only in the cortical region. The structures evaluated in previous studies included glomeruli, tubules, and cortical renal interstitium (5,7,20). As the RAS is important for renal development and AT 1 receptor blockade induced rarefaction of renal vessels in the outer and inner medullas, the aim of our study was to evaluate changes in the medullary region and to correlate structural abnormalities with functional changes, and to evaluate the ability of calcitriol to mitigate these changes.…”

Section: Discussionmentioning

confidence: 99%

“…The litter was reduced to six per mother to ensure equal feeding. During lactation, rats were divided into the following groups: (1) offspring of mothers treated with 2% sucrose solution during lactation and (2) offspring of mothers treated with losartan during lactation (100 mg/kg/day; All Chemistry, Brazil) (5,7). Each group received the treatment solutions in place of drinking water.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

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Effect of Calcitriol on the Renal Microvasculature Differentiation Disturbances Induced by AT1 Blockade During Nephrogenesis in Rats

et al. 2020

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Alterations in the renal vasculature during fetal programming can cause disturbances in renal structure and function that persist into adulthood. Calcitriol can affect cellular differentiation and proliferation, and promote endothelial cell maintenance, each of which is a key event in nephrogenesis. Calcitriol is a negative endocrine regulator of the renin gene. Rats exposed to renin-angiotensin system (RAS) antagonists during lactation have been shown to develop renal disorders, which demonstrated that the RAS may play an important role in mammalian kidney development. We evaluated the effects of calcitriol administration on losartan [angiotensin II receptor antagonist (ANGII), AT 1 ]-induced changes in renal differentiation in rats during lactation. Rats treated with losartan showed alterations in renal function and structure that persisted into adulthood. These disruptions included hydronephrosis, papillary atrophy, endothelial dysfunction, and aberrant endothelial structure. These changes were mitigated by treatment with calcitriol. The results of our study showed that animals exposed to AT 1 blockade during lactation exhibited altered renal microvasculature differentiation in adulthood that was attenuated by treatment with calcitriol.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Animals and Experimental Designmentioning

confidence: 99%

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Effect of Calcitriol on the Renal Microvasculature Differentiation Disturbances Induced by AT1 Blockade During Nephrogenesis in Rats

et al. 2020

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Neuroendocrine Regulation of Hydromineral Homeostasis

Mecawi

Ruginsk

Elias

et al. 2015

Comprehensive Physiology

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Since the crucial evolutionary change from an aqueous to a terrestrial environment, all living organisms address the primordial task of equilibrating the ingestion/production of water and electrolytes (primarily sodium) with their excretion. In mammals, the final route for the excretion of these elements is mainly through the kidneys, which can eliminate concentrated or diluted urine according to the requirements. Despite their primary role in homeostasis, the kidneys are not able to recover water and solutes lost through other systems. Therefore, the selective stimulation or inhibition of motivational and locomotor behavior becomes essential to initiate the search and acquisition of water and/or sodium from the environment. Indeed, imbalances affecting the osmolality and volume of body fluids are dramatic challenges to the maintenance of hydromineral homeostasis. In addition to behavioral changes, which are integrated in the central nervous system, most of the systemic responses recruited to restore hydroelectrolytic balance are accomplished by coordinated actions of the cardiovascular, autonomic and endocrine systems, which determine the appropriate renal responses. The activation of sequential and redundant mechanisms (involving local and systemic factors) produces accurate and self-limited effector responses. From a physiological point of view, understanding the mechanisms underlying water and sodium balance is intriguing and of great interest for the biomedical sciences. Therefore, the present review will address the biophysical, evolutionary and historical perspectives concerning the integrative neuroendocrine control of hydromineral balance, focusing on the major neural and endocrine systems implicated in the control of water and sodium balance.

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