The University of Southampton
University of Southampton Institutional Repository

Cardiac protection by oral sodium thiosulfate in a rat model of L-NNA-induced heart disease

Cardiac protection by oral sodium thiosulfate in a rat model of L-NNA-induced heart disease
Cardiac protection by oral sodium thiosulfate in a rat model of L-NNA-induced heart disease

Hypertension contributes to cardiac damage and remodeling. Despite the availability of renin-angiotensin system inhibitors and other antihypertensive therapies, some patients still develop heart failure. Novel therapeutic approaches are required that are effective and without major adverse effects. Sodium Thiosulfate (STS), a reversible oxidation product of hydrogen sulfide (H2S), is a promising pharmacological entity with vasodilator and anti-oxidant potential that is clinically approved for the treatment of calciphylaxis and cyanide poisoning. We hypothesized that Sodium Thiosulfate improves cardiac disease in an experimental hypertension model and sought to investigate its cardioprotective effects by direct comparison to the ACE-inhibitor lisinopril, alone and in combination, using a rat model of chronic nitric oxide (NO) deficiency. Systemic nitric oxide production was inhibited in Sprague Dawley rats by administering N-ω-nitro-l-arginine (L-NNA) with the food for three weeks, leading to progressive hypertension, cardiac dysfunction and remodeling. We observed that STS, orally administered via the drinking water, ameliorated L-NNA-induced heart disease. Treatment with STS for two weeks ameliorated hypertension and improved systolic function, left ventricular hypertrophy, cardiac fibrosis and oxidative stress, without causing metabolic acidosis as is sometimes observed following parenteral administration of this drug. STS and lisinopril had similar protective effects that were not additive when combined. Our findings indicate that oral intervention with a H2S donor such as STS has cardioprotective properties without noticeable side effects.

1663-9812
Nguyen, Isabel T.N.
706981b5-633b-4627-820a-767c0bc58aa9
Wiggenhauser, Lucas M.
7284952a-d988-48d6-89ca-cbcae36c3a8e
Bulthuis, Marian
c3831730-6a1a-41fa-850b-0324defca7ad
Hillebrands, Jan-Luuk
25949d83-4132-42aa-bb3c-c710cb5e8d1b
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Verhaar, Marianne C.
579ef89f-ed6f-47f8-aa53-a933e35ea089
van Goor, Harry
fadc9a49-233e-40c3-9e05-8713ffbc02e5
Joles, Jaap A.
911a0118-2e68-471f-9f54-7662d77f725d
Nguyen, Isabel T.N.
706981b5-633b-4627-820a-767c0bc58aa9
Wiggenhauser, Lucas M.
7284952a-d988-48d6-89ca-cbcae36c3a8e
Bulthuis, Marian
c3831730-6a1a-41fa-850b-0324defca7ad
Hillebrands, Jan-Luuk
25949d83-4132-42aa-bb3c-c710cb5e8d1b
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Verhaar, Marianne C.
579ef89f-ed6f-47f8-aa53-a933e35ea089
van Goor, Harry
fadc9a49-233e-40c3-9e05-8713ffbc02e5
Joles, Jaap A.
911a0118-2e68-471f-9f54-7662d77f725d

Nguyen, Isabel T.N., Wiggenhauser, Lucas M., Bulthuis, Marian, Hillebrands, Jan-Luuk, Feelisch, Martin, Verhaar, Marianne C., van Goor, Harry and Joles, Jaap A. (2021) Cardiac protection by oral sodium thiosulfate in a rat model of L-NNA-induced heart disease. Frontiers in Pharmacology, 12. (doi:10.3389/fphar.2021.650968).

Record type: Article

Abstract

Hypertension contributes to cardiac damage and remodeling. Despite the availability of renin-angiotensin system inhibitors and other antihypertensive therapies, some patients still develop heart failure. Novel therapeutic approaches are required that are effective and without major adverse effects. Sodium Thiosulfate (STS), a reversible oxidation product of hydrogen sulfide (H2S), is a promising pharmacological entity with vasodilator and anti-oxidant potential that is clinically approved for the treatment of calciphylaxis and cyanide poisoning. We hypothesized that Sodium Thiosulfate improves cardiac disease in an experimental hypertension model and sought to investigate its cardioprotective effects by direct comparison to the ACE-inhibitor lisinopril, alone and in combination, using a rat model of chronic nitric oxide (NO) deficiency. Systemic nitric oxide production was inhibited in Sprague Dawley rats by administering N-ω-nitro-l-arginine (L-NNA) with the food for three weeks, leading to progressive hypertension, cardiac dysfunction and remodeling. We observed that STS, orally administered via the drinking water, ameliorated L-NNA-induced heart disease. Treatment with STS for two weeks ameliorated hypertension and improved systolic function, left ventricular hypertrophy, cardiac fibrosis and oxidative stress, without causing metabolic acidosis as is sometimes observed following parenteral administration of this drug. STS and lisinopril had similar protective effects that were not additive when combined. Our findings indicate that oral intervention with a H2S donor such as STS has cardioprotective properties without noticeable side effects.

Text
fphar-12-650968 - Version of Record
Available under License Creative Commons Attribution.
Download (2MB)

More information

Accepted/In Press date: 11 March 2021
Published date: 15 April 2021

Identifiers

Local EPrints ID: 456213
URI: http://eprints.soton.ac.uk/id/eprint/456213
ISSN: 1663-9812
PURE UUID: e6d703ff-a64d-446a-b27b-c21f52ef3685
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 26 Apr 2022 17:48
Last modified: 17 Mar 2024 03:27

Export record

Altmetrics

Contributors

Author: Isabel T.N. Nguyen
Author: Lucas M. Wiggenhauser
Author: Marian Bulthuis
Author: Jan-Luuk Hillebrands
Author: Martin Feelisch ORCID iD
Author: Marianne C. Verhaar
Author: Harry van Goor
Author: Jaap A. Joles

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×