title: Alteration of ATP-sensitive K+ channels in rabbit aortic smooth muscle during left ventricular hypertrophy.
abstract: We investigated the impairment of ATP-sensitive K(+) (K(ATP)) channels in aortic smooth muscle cells (ASMCs) from isoproterenol-induced hypertrophied rabbits. The amplitude of K(ATP) channels induced by the K(ATP) channel opener pinacidil (10 μM) was greater in ASMCs from control than from hypertrophied animals. In phenylephrine-preconstricted aortic rings, pinacidil induced relaxation in a dose-dependent manner. The dose-dependent curve was shifted to the right in the hypertrophied (EC(50): 17.80 ± 3.28 μM) compared with the control model (EC(50): 6.69 ± 2.40 μM). Although the level of Kir6.2 subtype expression did not differ between ASMCs from the control and hypertrophied models, those of the Kir6.1 and SUR2B subtypes were decreased in the hypertrophied model. Application of the calcitonin-gene related peptide (100 nM) and adenylyl cyclase activator forskolin (10 μM), which activates protein kinase A (PKA) and consequently K(ATP) channels, induced a K(ATP) current in both control and hypertrophied animals; however, the K(ATP) current amplitude did not differ between the two groups. Furthermore, PKA expression was not altered between the control and hypertrophied animals. These results suggests that the decreased K(ATP) current amplitude and K(ATP) channel-induced vasorelaxation in the hypertrophied animals were attributable to the reduction in K(ATP) channel expression but not to changes in the intracellular signaling mechanism that activates the K(ATP) current.
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Hong
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Jeong
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D054086:KATP Channels / Q000819:agonists / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009924:Organ Culture Techniques; D020110:Pinacidil / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D054086:KATP Channels; C092520:uK-ATP-1 potassium channel; D020110:Pinacidil