title: Dopamine treatment attenuates acute kidney injury in a rat model of deep hypothermia and rewarming - The role of renal H2S-producing enzymes.
abstract: Hypothermia and rewarming produces organ injury through the production of reactive oxygen species. We previously found that dopamine prevents hypothermia and rewarming-induced apoptosis in cultured cells through increased expression of the H2S-producing enzyme cystathionine β-Synthase (CBS). Here, we investigate whether dopamine protects the kidney in deep body cooling and explore the role of H2S-producing enzymes in an in vivo rat model of deep hypothermia and rewarming. In anesthetized Wistar rats, body temperature was decreased to 15°C for 3h, followed by rewarming for 1h. Rats (n≥5 per group) were treated throughout the procedure with vehicle or dopamine infusion, and in the presence or absence of a non-specific inhibitor of H2S-producing enzymes, amino-oxyacetic acid (AOAA). Kidney damage and renal expression of three H2S-producing enzymes (CBS, CSE and 3-MST) was quantified and serum H2S level measured. Hypothermia and rewarming induced renal damage, evidenced by increased serum creatinine, renal reactive oxygen species production, KIM-1 expression and influx of immune cells, which was accompanied by substantially lowered renal expression of CBS, CSE, and 3-MST and lowered serum H2S levels. Infusion of dopamine fully attenuated renal damage and maintained expression of H2S-producing enzymes, while normalizing serum H2S. AOAA further decreased the expression of H2S-producing enzymes and serum H2S level, and aggravated renal damage. Hence, dopamine preserves renal integrity during deep hypothermia and rewarming likely by maintaining the expression of renal H2S-producing enzymes and serum H2S.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: George J
authors.initials: GJ
authors.lastname: Dugbartey
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Talaei
authors.affiliation: Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Houwertjes
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Goris
authors.affiliation: Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Epema
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hjalmar R
authors.initials: HR
authors.lastname: Bouma
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: r.h.henning@umcg.nl.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Henning
mesh_terms: D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000768:Anesthesia, General; D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000097:blood / Q000378:metabolism*; D007035:Hypothermia / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000293:injuries* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017694:Rewarming / Q000009:adverse effects*
chemical_list: D004791:Enzyme Inhibitors; D000625:Aminooxyacetic Acid; D004298:Dopamine; D006862:Hydrogen Sulfide
keywords: Acute kidney injury; Aminooxyacetic acid (PubChem CID: 286); Cystathionine beta synthase; Dopamine; Dopamine (PubChem CID: 65340); Hydrogen sulfide; Hypothermia; Reactive oxygen species