Captopril related kidney damage: renal afferent arteriolar responses to angiotensin II and inflammatory signaling.
- Author:
Su-Han ZHOU
1
;
Qian HUANG
1
;
Ying ZHOU
2
;
Xiao-Xia CAI
3
;
Yu CUI
1
;
Qin ZHOU
1
;
Jie GUO
1
;
Shan JIANG
1
;
Nan XU
1
;
Jiang-Hua CHEN
1
;
Ling-Li LI
4
;
En-Yin LAI
5
;
Liang ZHAO
6
Author Information
1. Kidney Disease Center of First Affiliated Hospital, and Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310003, China.
2. Department of Pharmacology, Gannan Healthcare Vocational College, Ganzhou 341000, China.
3. School of Basic Medical Sciences, Honghe Health Vocational College, Mengzi 661199, China.
4. Division of Nephrology and Hypertension, Georgetown University, Washington DC 20007, USA.
5. Kidney Disease Center of First Affiliated Hospital, and Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310003, China. laienyin@zju.edu.cn.
6. National Clinical Research Center for Child Health, National Children's Regional Medical Center, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China. 125752197@qq.com.
- Publication Type:Journal Article
- MeSH:
Angiotensin II/pharmacology*;
Animals;
Arterioles/metabolism*;
Captopril/pharmacology*;
Hydrogen Peroxide/pharmacology*;
Kidney;
Mice
- From:
Acta Physiologica Sinica
2022;74(1):125-133
- CountryChina
- Language:English
-
Abstract:
Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H2O2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT1R) and AT2R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H2O2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H2O2. The mRNAs of renal microvascular AT1R and AT2R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.
