Details

Autor(en) / Beteiligte

• Huang, Pan
• Chen, Siyao
• Wang, Yuan
• Liu, Jia
• Yao, Qiuyu
• Huang, Yaqian
• Li, Hongxia
• Zhu, Mingzhu
• Wang, Suxia
• Li, Lin
• Tang, Chaoshu
• Tao, Yinghong
• Yang, Guosheng
• Du, Junbao
• Jin, Hongfang

Titel

Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats

Ist Teil von

• Nitric oxide, 2015-04, Vol.46, p.192-203

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• •High-salt downregulated renal H2S generation in salt-sensitive Dahl rats.•H2S donor prevented salt-sensitive hypertension and activation of the RAS system.•HIF-1α mediated high-salt-induced inhibition of renal CBS/H2S pathway in Dahl rats. The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats. 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. 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. Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension.