title: Differential mechanisms for insulin-induced relaxations in mouse posterior tibial arteries and main mesenteric arteries.
abstract: The characteristics of endothelium-dependent relaxations in response to insulin and acetylcholine (ACh) in the mouse posterior tibial artery (PTA) were studied on wire myograph, and compared to those in the mouse main mesenteric artery (MMA). Insulin-induced relaxation in PTA was reversed by PI3K and Akt inhibitors, LY294002 and triciribine, but not by nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) or guanylate cyclase inhibitor, ODQ. The relaxation in PTA was also inhibited by apamin (small-conductance Ca(2+)-activated K(+) channel blocker) plus charybdotoxin (intermediate-conductance Ca(2+)-activated K(+) channel blocker), elevated KCl or ouabain (Na(+)-K(+) ATPase inhibitor) plus BaCl(2) [inwardly rectifying K(+) (K(IR)) channel inhibitor]; whereas L-NAME but not triciribine inhibited ACh-induced relaxation in PTA. On the other hand, nitric oxide and endothelium-derived hyperpolarizing factor albeit to a less extent mediated both insulin- and ACh-induced relaxations in MMA. The present study is for the first time dissecting out the components of endothelium-dependent relaxation in mouse PTA and suggesting differential responses to different agonists in distinctive blood vessels.
authors.affiliation: Institute of Vascular Medicine, Shenzhen Research Institute, No. 10, 2nd Yuexing Road, Nanshan District, Shenzhen, PR China; Li Ka Shing Institute of Health Sciences, Li Ka Shing Medical Sciences Building, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China. Electronic address: dandelionqu@gmail.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Qu
authors.affiliation: Institute of Vascular Medicine, Shenzhen Research Institute, No. 10, 2nd Yuexing Road, Nanshan District, Shenzhen, PR China; Li Ka Shing Institute of Health Sciences, Li Ka Shing Medical Sciences Building, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China. Electronic address: willian85@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Vascular Medicine, Shenzhen Research Institute, No. 10, 2nd Yuexing Road, Nanshan District, Shenzhen, PR China; Li Ka Shing Institute of Health Sciences, Li Ka Shing Medical Sciences Building, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China. Electronic address: b162714@mailserv.cuhk.edu.hk.
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Lau
authors.affiliation: Institute of Vascular Medicine, Shenzhen Research Institute, No. 10, 2nd Yuexing Road, Nanshan District, Shenzhen, PR China; Li Ka Shing Institute of Health Sciences, Li Ka Shing Medical Sciences Building, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China. Electronic address: yu-huang@cuhk.edu.hk.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001685:Biological Factors / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D016909:Tibial Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D007328:Insulin; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin; C026512:arginine methyl ester; D009569:Nitric Oxide; D010042:Ouabain; D001120:Arginine; D019869:Phosphatidylinositol 3-Kinases; D006162:Guanylate Cyclase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester
keywords: Apamin (PubChem CID:16218850); BaCl(2) (PubChem CID:25204); Charybdotoxin (PubChem CID:56842037); Endothelium-derived hyperpolarizing factor; Indomethacin (PubChem CID:3715); L-NAME (PubChem CID:39836); LY294002 (PubChem CID:3973); Main mesenteric artery; Mouse; Nitric oxide; ODQ (PubChem CID:1456); Ouabain (PubChem CID:439501); Posterior tibial artery; Triciribine (PubChem CID:24994886)