Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H2S Inhibition.

Pan Huang,Hongfang Jin,Heng Zhang,Boyang Lv,Dingfang Bu,Guang Wang,Junbao Du,Jia Liu,Guosheng Yang,Yaqian Huang,Yinghong Tao,Albino Carrizzo

doi:10.1155/2021/5530907

Abstract

Although taurine is known to exert an antihypertensive effect, it is unclear whether it is involved in the mechanism for hypertension-related target organ injury. To reveal the role of endogenous taurine in renal injury formation during salt-sensitive hypertension and clarify its mechanisms, both salt-sensitive Dahl rats and salt-resistant SS-13BN rats were fed a high-salt diet (8% NaCl) and given 2% taurine for 6 weeks. Rat systolic blood pressure (SBP) was measured by the tail-cuff method and artery catheterization. Kidney ultrastructure was observed under an electron microscope. Taurine content and mRNA and protein levels of taurine synthases, cysteine dioxygenase type 1 (CDO1) and cysteine sulfinic acid decarboxylase (CSAD), were decreased in Dahl rats fed a high-salt diet. However, taurine supplementation and the resulting increase in renal taurine content reduced the increased SBP and improved renal function and structural damage in high-salt diet-fed Dahl rats. In contrast, taurine did not affect SS-13BN SBP and renal function and structure. Taurine intervention increased the renal H2S content and enhanced cystathionine-β-synthase (CBS) expression and activity in Dahl rats fed a high-salt diet. Taurine reduced the renin, angiotensin II, and aldosterone contents and the levels of oxidative stress indices in Dahl rat renal tissues but increased antioxidant capacity, antioxidant enzyme activity, and protein expression. However, taurine failed to achieve this effect in the renal tissue of SS-13BN rats fed a high-salt diet. Pretreatment with the CBS inhibitor HA or renal CBS knockdown inhibited H2S generation and subsequently blocked the effect of taurine on renin, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) levels in high-salt-stimulated Dahl renal slices. In conclusion, the downregulation of endogenous taurine production resulted in a decrease in the renal CBS/H2S pathway. This decrease subsequently promoted renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress in the kidney, ultimately contributing to renal injury in salt-sensitive Dahl rats.

Highlights

The kidney is the main target of organ damage due to hypertension
Antibodies against CBS, mercaptopyruvate sulfurtransferase (MPST), gp91phox, p47phox, p22phox and CD31 were purchased from Santa Cruz (Dallas, TX, USA); CSE antibody was purchased from Sigma-Aldrich; antibodies against cysteine sulfinic acid decarboxylase (CSAD), cysteine dioxygenase type 1 (CDO1), CD31 and renin were purchased from Abcam (Waltham, MA, USA); β-actin antibody was purchased from Beijing Zhongshan Golden Bridge Biotechnology Co., Ltd. (Beijing, China); GAPDH antibody was from Shanghai Kangcheng Biological Engineering Company (Shanghai, China), and antibodies against superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) were purchased from Enzo Life (Farmingdale, NY, USA)
Taurine can lower blood pressure, reduce the levels of vasoconstrictor active substances, and upregulate vasodilator substance content in Wistar rats with hypertension induced by abdominal aortic stenosis and HS [45]; these results suggest that taurine inhibits the occurrence of renal hypertension possibly through regulating the levels of vasoactive substances

Summary

Introduction

The kidney is the main target of organ damage due to hypertension. A chronic increase in arterial pressure leads to a decrease in the glomerular filtration rate, proteinuria, and renal failure [1]. Chronic kidney disease, which is caused by hypertension, is a powerful independent risk factor for adverse cardiovascular outcomes [2]. The pathogenesis of hypertensive renal injury is still poorly understood. Dietary habits are closely related to the incidence of hypertension [3]. Up to 50% of patients with essential hypertension have high salt-induced hypertension, known as salt-sensitive hypertension [4]. Saltsensitive hypertensive patients are more likely to develop end-stage renal disease compared with salt-resistant hypertensive patients [5].

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Discussion

Conclusion