title: Sodium thiosulfate attenuates angiotensin II-induced hypertension, proteinuria and renal damage.
abstract: Hypertension and proteinuria are important mediators of renal damage. Despite therapeutic interventions, the number of patients with end stage renal disease steadily increases. Hydrogen sulfide (H(2)S) is an endogenously produced gasotransmitter with vasodilatory, anti-inflammatory and antioxidant properties. These beneficial characteristics make H(2)S an attractive candidate for pharmacological use in hypertensive renal disease. We investigated the protective properties of H(2)S in angiotensin II (Ang II)-induced hypertensive renal disease in rats. Treatment with the H(2)S donor NaHS and major H(2)S metabolite sodium thiosulfate (STS) during three weeks of Ang II infusion reduced hypertension, proteinuria, oxidative stress and renal functional and structural deterioration. In an ex vivo isolated perfused kidney setup, NaHS, but not STS, reduced intrarenal pressure. The effect of NaHS could partially be explained by its activation of the ATP-sensitive potassium channels. In conclusion, treatment with H(2)S attenuates Ang II-associated functional and structural renal deterioration, suggesting that intervention in H(2)S production pathways has potential therapeutic benefit and might be a valuable addition to the already existing antihypertensive and renoprotective therapies.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Snijder
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Anne-Roos S
authors.initials: AR
authors.lastname: Frenay
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Koning
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bachtler
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pasch
authors.affiliation: Kidney Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.affiliation: Kidney Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Else
authors.initials: E
authors.lastname: van den Berg
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Eelke M
authors.initials: EM
authors.lastname: Bos
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.affiliation: Kidney Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: h.van.goor@umcg.nl.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006973:Hypertension / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects*; D011507:Proteinuria / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013885:Thiosulfates / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D013885:Thiosulfates; D000804:Angiotensin II; C017717:sodium thiosulfate
keywords: Angiotensin II; Fibrosis; Hydrogen sulfide; Proteinuria; Thiosulfate