Pan Huang1, Siyao Chen1, Yuan Wang1, Jia Liu1, Qiuyu Yao1, Yaqian Huang1, Hongxia Li1, Mingzhu Zhu1, Suxia Wang2, Lin Li3, Chaoshu Tang4, Yinghong Tao5, Guosheng Yang5, Junbao Du6, Hongfang Jin7. 1. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. 2. Lab of Electric Microscopy, Peking University First Hospital, Beijing 100034, China. 3. Central Laboratory, Peking University First Hospital, Beijing 100034, China. 4. Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China; Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing 100191, China. 5. Animal Center, Peking University First Hospital, Beijing, 100034, China. 6. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China; Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China. 7. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Electronic address: jinhongfang51@126.com.
Abstract
BACKGROUND: The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats. METHODS: High-salt-induced hypertension rat model was made by feeding Dahl rat high-salt diet containing 8% NaCl for 8 weeks with SD rats as control. SBP and aorta structure in rats were observed. Endogenous H2S content and expression of cystathionine β-lyase (CBS), cystathionine γ-lyase and mercaptopyruvate sulfurtransferase in renal tissues were detected. Mechanisms for the impact of high-salt on CBS/H2S in renal tissues were studied, targeting HIF-1α pathway. The effect of H2S on RAS in serum and renal tissue of rats were tested. RESULTS: High-salt reduced endogenous H2S content and inhibited the expression of CBS in renal tissue in salt-sensitive Dahl rats. H2S donor, however, inhibited salt-sensitive hypertension, reversed aortic structural remodeling and inhibited activation of the RAS system in renal tissues in Dahl rats. Expression of HIF-1α was decreased but expression of PHD2 was increased in renal tissue of Dahl rats with high-salt diet, whereas they did not alter in renal tissue of SD rats with high-salt diet. Ex vivo experiment showed that inhibitor of HIF-1α degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl rats with high-salt. In contrast, inhibitor of HIF-1α activity decreased the CBS/H2S pathway in the renal tissue of SD rats treated with high-salt. CONCLUSIONS: Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension.
BACKGROUND: The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats. METHODS: High-salt-induced hypertensionrat model was made by feeding Dahl rat high-salt diet containing 8% NaCl for 8 weeks with SD rats as control. SBP and aorta structure in rats were observed. Endogenous H2S content and expression of cystathionine β-lyase (CBS), cystathionine γ-lyase and mercaptopyruvate sulfurtransferase in renal tissues were detected. Mechanisms for the impact of high-salt on CBS/H2S in renal tissues were studied, targeting HIF-1α pathway. The effect of H2S on RAS in serum and renal tissue of rats were tested. RESULTS: High-salt reduced endogenous H2S content and inhibited the expression of CBS in renal tissue in salt-sensitive Dahl rats. H2Sdonor, however, inhibited salt-sensitive hypertension, reversed aortic structural remodeling and inhibited activation of the RAS system in renal tissues in Dahl rats. Expression of HIF-1α was decreased but expression of PHD2 was increased in renal tissue of Dahl rats with high-salt diet, whereas they did not alter in renal tissue of SD rats with high-salt diet. Ex vivo experiment showed that inhibitor of HIF-1α degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl rats with high-salt. In contrast, inhibitor of HIF-1α activity decreased the CBS/H2S pathway in the renal tissue of SD rats treated with high-salt. CONCLUSIONS: Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension.