Nguyen Isabel T N, Klooster Astrid, Minnion Magdalena, Feelisch Martin, Verhaar Marianne C, van Goor Harry, Joles Jaap A
Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
Kidney Int. 2020 Aug;98(2):366-377. doi: 10.1016/j.kint.2020.02.020. Epub 2020 Mar 23.
Sodium thiosulfate, a reversible oxidation product of hydrogen sulfide, has vasodilating and anti-oxidative properties, making it an attractive agent to alleviate damaging effects of hypertension. In experimental settings, inhibition of nitric oxide synthase causes hypertension, renal dysfunction and damage. We hypothesized that thiosulfate would attenuate renal injury and improve renal function, hemodynamics and the efficiency of oxygen utilization for sodium reabsorption in hypertensive renal disease. Additionally, thiosulfate co-administration would further improve these variables when compared to inhibiting the renin-angiotensin system alone. Nitric oxide synthase was inhibited in Sprague Dawley rats by administering N-ω-nitro-L-arginine (L-NNA) in the food for three weeks. After one week, rats were split into two groups; without and with thiosulfate in the drinking water. In a parallel study, rats given N-ω-nitro-L-arginine and the angiotensin converting enzyme inhibitor lisinopril at a relatively low dose in their food were divided into two groups; without and with thiosulfate in the drinking water. Treatment with thiosulfate alleviated hypertension (mean 190 vs. 229 mmHg), lowered plasma urea (mean 11.3 vs. 20.0 mmol/L) and improved the terminal glomerular filtration rate (mean 503 vs. 260 μl/min/100 gbw), effective renal plasma flow (mean 919 vs. 514 μl/min/100 gbw) and oxygen utilization for sodium reabsorption (mean 14.3 vs. 8.6 μmol/μmol). Combining thiosulfate with lisinopril further lowered renal vascular resistance (mean 43 vs. 63 mmHg/ml/min/100 gbw) and prevented glomerulosclerosis. Thus, our results suggest that thiosulfate has therapeutic potential in hypertensive renal disease and might be of value when added to standard antihypertensive therapies.
硫代硫酸钠是硫化氢的一种可逆氧化产物，具有血管舒张和抗氧化特性，使其成为缓解高血压损害作用的一种有吸引力的药物。在实验环境中，抑制一氧化氮合酶会导致高血压、肾功能障碍和损伤。我们假设硫代硫酸钠会减轻肾损伤，改善肾功能、血流动力学以及高血压肾病中钠重吸收的氧利用效率。此外，与单独抑制肾素 - 血管紧张素系统相比，联合使用硫代硫酸钠会进一步改善这些变量。通过在食物中给予N - ω - 硝基 - L - 精氨酸（L - NNA）三周，抑制Sprague Dawley大鼠的一氧化氮合酶。一周后，将大鼠分为两组；一组饮用水中不加硫代硫酸钠，另一组添加硫代硫酸钠。在一项平行研究中，在食物中给予N - ω - 硝基 - L - 精氨酸和相对低剂量血管紧张素转换酶抑制剂赖诺普利的大鼠被分为两组；一组饮用水中不加硫代硫酸钠，另一组添加硫代硫酸钠。硫代硫酸钠治疗可缓解高血压（平均190对229 mmHg），降低血浆尿素（平均11.3对20.0 mmol/L），并改善终末期肾小球滤过率（平均503对260 μl/min/100 gbw）、有效肾血浆流量（平均919对514 μl/min/100 gbw）以及钠重吸收的氧利用（平均14.3对8.6 μmol/μmol）。将硫代硫酸钠与赖诺普利联合使用可进一步降低肾血管阻力（平均43对63 mmHg/ml/min/100 gbw）并预防肾小球硬化。因此，我们的结果表明硫代硫酸钠在高血压肾病中具有治疗潜力，并且在添加到标准抗高血压治疗中可能具有价值。
