Rho kinase regulates renal blood flow by modulating eNOS activity in ischemia-reperfusion of the rat kidney.
Renal ischemia-reperfusion (I/R) results in vascular dysfunction characterized by a reduced endothelium-dependent vasodilatation and subsequently impaired blood flow. In this study, we investigated the role of Rho kinase in endothelial nitric oxide synthase (eNOS)-mediated regulation of renal blood flow and vasomotor tone in renal I/R. Male Wistar rats were subjected to 60-min bilateral clamping of the renal arteries or sham procedure. One hour before the clamping, the Rho kinase inhibitor Y27632 (1 mg/kg) was intravenously infused. After I/R, renal blood flow was measured using fluorescent microspheres. I/R resulted in a 62% decrease in renal blood flow. In contrast, the blood flow decrease in the group treated with the Rho kinase inhibitor (YI/R) was prevented. Endothelium-dependent vasodilatation of renal arcuate arteries to ACh was measured ex vivo in a pressure myograph. These experiments demonstrated that the in vivo treatment with the Rho kinase inhibitor prevented the decrease in the nitric oxide (NO)-mediated vasodilator response. In addition, after I/R renal interlobar arteries showed a decrease in phosphorylated eNOS and vasodilator-stimulated phosphoprotein, a marker for bioactive NO, which was attenuated by in vivo Rho kinase inhibition. These findings indicate that in vivo inhibition of Rho kinase in renal I/R preserves renal blood flow by improving eNOS function.
Versteilen
Amanda M G
AM
Laboratory for Physiology, Faculty of Medicine, VU University Medical Center, De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands. amg.versteilen@vumc.nl
Korstjens
Iolente J M
IJ
Musters
René J P
RJ
Groeneveld
A B Johan
AB
Sipkema
Pieter
P
D000109:Acetylcholine / Q000097:blood; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006439:Hemodynamics; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000201:enzymology; D012079:Renal Circulation / Q000502:physiology*; D015427:Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D054460:rho-Associated Kinases; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine