Background: Dopamine, via activation of D1-like and D2-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 microg/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 alpha1 subunit expression, and p44/42 MAPK phosphorylation were measured.
Results: We found extensive necrosis, apoptosis, and decreased NKA activity (with no change in alpha1 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 D1-like receptor agonist, may protect against I/R injury to proximal tubules of the kidney, via p44/42 MAPK activation.