UNASSIGNED: The protective effects of @entity1920 -activated protein kinase (AMPK) on the @entity209 may include direct effects on resistance artery vasomotor function. However, the precise actions of AMPK on microvessels and their potential interaction are largely unknown. Thus, we set to determine the effects of AMPK activation on vascular smooth muscle tone and the underlying mechanisms. Resistance arteries isolated from hamster and @entity19 exhibited a pronounced endothelium-independent dilation on direct pharmacological AMPK activation by 2 structurally unrelated compounds (PT1 and @entity48822 ). The dilation was associated with a decrease of intracellular-free @entity460 [ @entity141 ]i in vascular smooth muscle cell. AMPK stimulation induced activation of @entity4029 channels as assessed by patch clamp studies in freshly isolated hamster vascular smooth muscle cell and confirmed by direct proof of membrane hyperpolarization in intact arteries. The @entity4029 channel blocker @entity19191 abolished the hyperpolarization but only partially reduced the dilation and did not affect the decrease of [ @entity141 ]i. By contrast, the sarcoplasmic/endoplasmic @entity141 -ATPase (SERCA) inhibitor @entity2426 largely reduced these effects, whereas combined inhibition of SERCA and @entity4029 channels virtually abolished them. AMPK stimulation significantly increased the phosphorylation of the SERCA modulator phospholamban at the regulatory T17 site. Stimulation of smooth muscle AMPK represents a new, potent vasodilator mechanism in resistance vessels. AMPK directly relaxes vascular smooth muscle cell by a decrease of [ @entity141 ]i. This is achieved by @entity460 sequestration via SERCA activation, as well as activation of @entity4029 channels. There is in part a mutual compensation of both @entity460 -lowering mechanisms. However, SERCA activation which involves an AMPK-dependent phosphorylation of phospholamban is the predominant mechanism in resistance vessels.

AMPK Dilates Resistance Arteries via Activation of SERCA and XXXX Channels in Smooth Muscle.

@entity48822 :: ('MESH:C512408', 'Chemical') :: ['A769662'] @entity4029 :: ('16531(Tax:10090)', 'Gene') :: ['BKCa'] @entity19191 :: ('MESH:C064719', 'Chemical') :: ['iberiotoxin'] @entity2426 :: ('MESH:D019284', 'Chemical') :: ['thapsigargin'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity1920 :: ('CHEBI:16027', 'Chemical') :: ["5'-AMP"] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity209 :: ('MESH:D008659', 'Disease') :: ['metabolic syndrome']
@entity4029 :: (16531(Tax:10090),Gene) :: ['BKCa']
