Role of cyclooxygenase and derived reactive oxygen species in rho-kinase-mediated impairment of endothelium-dependent vasodilation and blood flow after ischemia-reperfusion of the rat kidney.
OBJECTIVE
Decreased endothelium-dependent vasodilation and blood flow in renal ischemia-reperfusion (IR) may result in part from rho-kinase activation, and cyclooxygenase (COX) activation, and resultant reactive oxygen species (ROS) may be involved.


METHODS
We tested this hypothesis in male Wistar rats, subjected to 60 min of bilateral clamping of the renal arteries and 60 min of reperfusion or a sham procedure, and treated by the rho-kinase inhibitor Y27632 (1 mg/kg) and/or the nonspecific COX inhibitor diclofenac (10 mg/kg). Renal blood flow was measured by fluorescent microspheres, and ROS in the arterial endothelium was quantified by dihydroethidium staining. Endothelium-dependent vasodilation was determined by an acetylcholine concentration-response curve in the presence or absence of diclofenac (10 microM).


RESULTS
Y27632 increased renal blood flow and reduced ROS in vivo, and improved endothelium-dependent vasodilation in vitro, following IR with or without diclofenac. Following IR, diclofenac had no effect on renal blood flow and ROS in vivo, but improved endothelium-dependent vasodilation in vitro.


CONCLUSIONS
Activation of rho-kinase impairs endothelium-dependent vasodilation and perfusion following renal IR, independently of COX and resultant ROS. In contrast, the vasodilatory effect of rho-kinase inhibition may be partly mediated by decreasing ROS, unrelated to COX and resultant vasoconstricting prostanoids.
Versteilen
Amanda M G
AM
Laboratory for Physiology and Intensive Care Unit, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
Korstjens
Iolente J M
IJ
Musters
René J P
RJ
Groeneveld
A B Johan
AB
Sipkema
Pieter
P
D000818:Animals; D001783:Blood Flow Velocity; D004730:Endothelium, Vascular / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction; D014664:Vasodilation; D054460:rho-Associated Kinases / Q000378:metabolism*
D017382:Reactive Oxygen Species; D011451:Prostaglandin-Endoperoxide Synthases; D054460:rho-Associated Kinases