Losartan protects against intermittent hypoxia-induced peritubular capillary loss by modulating the renal renin-angiotensin system and angiogenesis factors

Autor: Jiqiang Wu, Yao Chu, Qin Yu, Zhenxiu Jiang
Rok vydání: 2019
Předmět:
Male
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Angiotensin receptor
Kidney Cortex
Angiogenesis
Renal cortex
Biophysics
030204 cardiovascular system & hematology
Protective Agents
Biochemistry
Losartan
Receptor
Angiotensin
Type 1
Renin-Angiotensin System
Thrombospondin 1
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Renin–angiotensin system
medicine
Animals
Rats
Wistar
Hypoxia
030304 developmental biology
0303 health sciences
Kidney
Sleep Apnea
Obstructive
business.industry
Angiotensin II
Body Weight
Epithelial Cells
General Medicine
Hypoxia-Inducible Factor 1
alpha Subunit
Capillaries
Rats
Vascular endothelial growth factor
medicine.anatomical_structure
Endocrinology
chemistry
Creatinine
Angiogenesis Inducing Agents
business
Angiotensin II Type 1 Receptor Blockers
medicine.drug
Zdroj: Acta biochimica et biophysica Sinica. 52(1)
ISSN: 1745-7270
Popis: Obstructive sleep apnea is characterized by chronic intermittent hypoxia (CIH), which is a risk factor for renal peritubular capillary (PTC) loss, and angiotensin II receptor blockers can alleviate PTC loss. However, the mechanism by which losartan (an angiotensin II receptor blocker) reduces CIH-induced PTC loss and attenuates kidney damage is still unknown. Thus, in this study, we examined the protective effects of losartan against CIH-induced PTC loss and explored the underlying mechanisms in rat CIH model. The immunohistochemical staining of CD34 and morphological examination showed that CIH reduced PTC density and damaged tubular epithelial cells. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR, and western blot analysis results revealed that CIH increased the expression of hypoxia inducible factor-1α (HIF-1α), angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R), pro-angiogenesis factor vascular endothelial growth factor (VEGF), and anti-angiogenesis factor thrombospondin-1 (TSP-1) in the renal cortex of rats. CIH may up-regulate VEGF expression and simultaneously increase TSP-1 production. By histopathological, immunohistochemistry, ELISA, RT-qPCR, and western blot analysis, we found that the expressions of renal renin-angiotensin system (RAS), HIF-1α, VEGF, and TSP-1 were decreased, and PTC loss and tubular epithelial cell injury were attenuated with losartan treatment. Losartan ameliorated CIH-induced PTC loss by modulating renal RAS to improve the crosstalk between endothelial cells and tubular epithelial cells and subsequently regulate the balance of angiogenesis factors. Our study provided novel insights into the mechanisms of CIH-induced kidney damage and indicated that losartan could be a potential therapeutic agent for renal protection by alleviating CIH-induced PTC loss.
Databáze: OpenAIRE
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