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


CONCLUSIONS
Therefore, bromocriptine, a D1-like receptor agonist, may protect against I/R injury to proximal tubules of the kidney, via p44/42 MAPK activation.
Narkar
Vihang
V
Heart and Kidney Institute College of Pharmacy, University of Houston, Houston, Texas 77204-5041, USA.
Kunduzova
Oksana
O
Hussain
Tahir
T
Cambon
Claudie
C
Parini
Angelo
A
Lokhandwala
Mustafa
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009336:Necrosis; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase