title: Cardiovascular responses to retigabine in conscious rats--under normotensive and hypertensive conditions.
abstract: OBJECTIVE
  Retigabine is a recently approved antiepileptic agent which activates Kv7.2-7.5 potassium channels. It is emerging that these channels have an important role in vascular regulation, but the vascular effects of retigabine in the conscious state are unknown. Hence, in the present study we assessed the regional haemodynamic responses to retigabine in conscious rats.
  
  
  METHODS
  Male Sprague Dawley rats were chronically instrumented with pulsed Doppler flow probes to measure regional haemodynamic responses to retigabine under control conditions and during acute hypertension induced by infusion of angiotensin II and arginine vasopressin. Further experiments were performed, using the β-adrenoceptor antagonists CGP 20712A, ICI 118551 and propranolol, to elucidate the roles of β-adrenoceptors in the responses to retigabine in vivo and in vitro.
  
  
  RESULTS
  Under normotensive conditions, retigabine induced dose-dependent hypotension and hindquarters vasodilatation, with small, transient renal and mesenteric vasodilatations. In the acutely hypertensive state, the renal and mesenteric, but not hindquarters, vasodilatations were enhanced. The response of the hindquarters vascular bed to retigabine was mediated, in part, by β₂-adrenoceptors. However, in vitro experiments confirmed that retigabine did not act as a β-adrenoceptor agonist.
  
  
  CONCLUSIONS
  We demonstrated that retigabine causes regionally specific vasodilatations, which are different under normotensive and hypertensive conditions, and are, in part, mediated by β₂-adrenoceptors in some vascular beds but not in others. These results broadly support previous findings and further indicate that Kv7 channels are a potential therapeutic target for the treatment of vascular diseases associated with inappropriate vasoconstriction.
authors.affiliation: Institute of Cell Signalling, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
authors.forename: L V
authors.initials: LV
authors.lastname: Fretwell
authors.forename: J
authors.initials: J
authors.lastname: Woolard
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D016466:CHO Cells; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects*; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D051656:KCNQ Potassium Channels / Q000819:agonists* / Q000378:metabolism; D051658:KCNQ2 Potassium Channel / Q000819:agonists* / Q000378:metabolism; D008297:Male; D049990:Membrane Transport Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010655:Phenylenediamines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: C553443:ADRB2 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents; D002219:Carbamates; D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; C496915:Kcnq2 protein, rat; C501028:Kcnq5 protein, rat; D049990:Membrane Transport Modulators; D010655:Phenylenediamines; D018343:Receptors, Adrenergic, beta-2; D011994:Recombinant Proteins; C101866:ezogabine