title: The new antihypertensive drug iptakalim activates ATP-sensitive potassium channels in the endothelium of resistance blood vessels.
abstract: OBJECTIVE
  To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs).
  
  
  METHODS
  Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips.
  
  
  RESULTS
  Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 μmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 μmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 μmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 μmol/L, and even ATPγS (1000 μmol/L) was infused into the cells.
  
  
  CONCLUSIONS
  Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.
authors.affiliation: Department of Environment and Pharmacy, Tianjin Institute of Health and Environmental Medicine, Beijing 100850, China.
authors.forename: Su-yang
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, China.
authors.forename: Wen-yu
authors.initials: WY
authors.lastname: Cui
authors.affiliation: Department of Environment and Pharmacy, Tianjin Institute of Health and Environmental Medicine, Beijing 100850, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D054086:KATP Channels; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines; D000255:Adenosine Triphosphate