Dopamine D2-like receptor agonist bromocriptine protects against ischemia/reperfusion injury in rat kidney

Background. Dopamine, via activation of D-1-like and D-2-like receptors, plays an important role in the regulation of renal sodium excretion. Recently, we demonstrated that dopamine D2-like receptor agonist (bromocriptine) stimulates p44/42 mitogen-activated protein kinases (MAPKs) and Na+ ,K+ ATPase (NKA) activity in proximal tubular epithelial cells. Since both these parameters are compromised in ischemia/reperfusion (I/R) injury to the kidney, we investigated whether bromocriptine protects against the injury. Methods. In this study we used unilateral rat model of renal I/R injury. The Sprague-Dawley rats were divided into vehicle and bromocriptine groups. The vehicle and bromocriptine group was treated with vehicle and bromocriptine (500 mug/kg intravenously), respectively, 15 minutes before the induction of unilateral ischemia followed by 24- or 48-hour reperfusion. At the end of 24 or 48 hours the animals were sacrificed to collect control and ischemic kidney cortices, in which necrosis, apoptosis, NKA activity, NKA a 1 subunit expression, and p44/42 MAPK phosphorylation were measured. Results. We found extensive necrosis, apoptosis, and decreased NKA activity (with no change in a 1 subunit) in the ischemic kidney cortex compared to the nonischemic cortex from the vehicle-treated rats as early as 24 hours post-reperfusion. In contrast, I/R injury-induced necrotic, apoptotic, and decrease in NKA activity were absent in the outer cortex of bromocriptine-treated rats after 24 or 48 hours. Interestingly, we detected significantly higher phosphorylation of p44/42 MAPKs in control and ischemic kidneys of bromocriptine-treated rats compared to those of vehicle-treated rats. Conclusion. Therefore, bromocriptine, a D-2-like receptor agonist, may protect against I/R injury to proximal tubules of the kidney, via p44/42 MAPK activation.