Visfatin causes endothelium-dependent relaxation in isolated blood vessels.
Visfatin is a novel adipocyte-derived cytokine. We hypothesized that visfatin could directly affect vascular reactivity. To test the hypothesis, effects of visfatin on contraction of isolated blood vessels were examined. In endothelium-intact rat aorta, pretreatment with visfatin (100 ng/ml, 30 min) inhibited noradrenaline (NA; 1 nM-1 microM)-induced contraction. In NA (100 nM)-pre-contracted aorta, visfatin (1-100 ng/ml) directly induced a relaxation. Although an N(G)-Nitro-L-arginine methyl ester (300 microM, 15 min) inhibited the relaxation, an insulin receptor inhibitor, AGL2263 (10 microM, 20 min) was ineffective. Visfatin (100 ng/ml, 20 min) induced a phosphorylation of eNOS at serine 1177 and a de-phosphorylation of eNOS at threonine 495. Visfatin also induced a phosphorylation of Akt at serine 473 and a substrate of cGMP-dependent protein kinase, vasodilator stimulated phosphoprotein at serine 239. Present study revealed for the first time that visfatin has a vasodilating effect on isolated blood vessels, which is mediated via endothelium-derived NO.
Yamawaki
Hideyuki
H
Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628 Japan. yamawaki@vmas.kitasato-u.ac.jp
Hara
Naoko
N
Okada
Muneyoshi
M
Hara
Yukio
Y
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D001583:Benzoxazoles / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014664:Vasodilation; D000098662:Vasodilator-Stimulated Phosphoprotein
C541021:AGL 2263; D001583:Benzoxazoles; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D002599:Chalcone; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D054409:Nicotinamide Phosphoribosyltransferase; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt