title: Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease.
abstract: BACKGROUND
  Cardiovascular disease is a leading cause of death in modern societies. Hyperpolarizing Ca(2+)-activated K(+) channels (K(Ca)) are important membrane proteins in the control of arterial tone and pathological vascular remodelling and thus could serve as new drug targets.
  
  
  METHODS
  We summarize recent advances in the field of vascular K(Ca) and their roles in cardiovascular pathologies such as hypertension and restenosis disease and draw attention to novel small-molecule channel modulators and their possible therapeutic utility. This review focuses on literature from the last four to five years.
  
  
  RESULTS
  Pharmacological opening of endothelial KCa3.1/KCa2.3 channels stimulates endothelium-derived-hyperpolarizing-factor-mediated arteriolar dilation and lowers blood pressure. Inhibition of smooth muscle KCa3.1 channels has beneficial effects in restenosis disease and atherosclerosis. We consider the therapeutic potential of KCa3.1/KCa2.3 openers as novel endothelium-specific antihypertensive drugs as well as of KCa3.1-blockers for the treatment of pathological vascular remodelling and discuss advantages and disadvantages of the pharmacotherapeutic approaches.
  
  
  CONCLUSIONS
  Pharmacological manipulation of vascular K(Ca) channels by novel small-molecule modulators offers new venues for alternative treatments of hypertension, restenosis and atherosclerosis. Additional efforts are required to optimize these compounds and to validate them as cardiovascular-protective drugs.
authors.affiliation: Institute of Medical Biology, Depatrment of Physiology, SDU, J.B. Winsløwsvej 21 3., 5000 Odense C, Denmark. rkohler@health.sdu.dk
authors.forename: Ralf
authors.initials: R
authors.lastname: Köhler
authors.forename: Brajesh P
authors.initials: BP
authors.lastname: Kaistha
authors.forename: Heike
authors.initials: H
authors.lastname: Wulff
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy*; D001685:Biological Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000187:drug effects / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D014652:Vascular Diseases / Q000188:drug therapy*; D014664:Vasodilation
chemical_list: D001685:Biological Factors; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C494841:KCNMA1 protein, human; C496923:KCNN4 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D024681:Potassium Channels, Calcium-Activated; C067410:endothelium-dependent hyperpolarization factor