Sodium thiosulfate improves renal function and oxygenation in L-NNA-induced hypertension in rats.

Abstract:

: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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Nguyen ITN,Klooster A,Minnion M,Feelisch M,Verhaar MC,van Goor H,Joles JA

doi

10.1016/j.kint.2020.02.020

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

366-377

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(20)30262-3

journal_volume

98

pub_type

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