Dopamine treatment attenuates acute kidney injury in a rat model of deep hypothermia and rewarming – The role of renal H2S-producing enzymes

• DOI: 10.1016/j.ejphar.2015.11.022
• Publication Date: 2015-11-21T04:40:25Z
• Authors: George J. Dugbartey; Fatemeh Talaei; Martin C. Houwertjes; Maaike Goris; Anne H. Epema; Hjalmar R. Bouma; Robert H. Henning
• Keywords: Male; Dopamine; ISCHEMIA-REPERFUSION INJURY; Hypothermia; ACCIDENTAL HYPOTHERMIA; Anesthesia, General; Kidney; Gene Expression Regulation, Enzymologic; 03 medical and health sciences; COLD-PRESERVATION; FAILURE; Animals; RECEPTOR AGONIST; Hydrogen Sulfide; OXIDATIVE STRESS; Enzyme Inhibitors; Rats, Wistar; Rewarming; Cystathionine beta synthase; 0303 health sciences; Hydrogen sulfide; TRANSPLANTATION; Hemodynamics; Aminooxyacetic Acid; HYDROGEN-SULFIDE PROTECTS; Acute kidney injury; Rats; 3. Good health; ISCHEMIA/REPERFUSION-INJURY; GRAFT FUNCTION; Reactive oxygen species

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.