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dc.contributor.authorFretwell, L.en
dc.contributor.authorWoolard, J.en
dc.date.accessioned2013-05-03T09:58:01Z
dc.date.available2013-05-03T09:58:01Z
dc.date.issued2013
dc.identifier.citationFretwell, L. and Woolard, J. (2013) Cardiovascular responses to retigabine in conscious rats - under normotensive and hypertensive conditions. British Journal of Pharmacology. online firsten
dc.identifier.urihttp://hdl.handle.net/2086/8418
dc.description.abstractBACKGROUND AND PURPOSE: Retigabine is a recently approved anti-epileptic agent which activates Kv7.2-7.5 potassium channels. An important role for these channels in vascular regulation is emerging, but the vascular effects of retigabine in the conscious state are unknown. In the present study the regional haemodynamic responses to retigabine were assessed in conscious rats. EXPERIMENTAL APPROACH: 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 (AII) and arginine vasopressin (AVP). Further experiments were performed to elucidate the roles of β-adrenoceptor activation in the responses to retigabine in vivo and in vitro. KEY RESULTS: Under normotensive conditions, retigabine caused 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 hindquarters response 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 AND IMPLICATIONS: These results, showing differential vasodilator effects of retigabine, broadly support other studies identifying Kv7 channels as mediators of vascular tone, highlighting the different responses under normotensive and hypertensive conditions, and a role for β-adrenoceptor activation.en
dc.description.sponsorshipFunded by a University of Nottingham Career Development Fellowshipen
dc.language.isoenen
dc.publisherWileyen
dc.subjectRetigabineen
dc.subjectKv7en
dc.subjectKCNQen
dc.subjecthypertensionen
dc.subjectβ-adrenoceptorsen
dc.subjecthaemodynamic responsesen
dc.subjectconscious ratsen
dc.titleCardiovascular responses to retigabine in conscious rats - under normotensive and hypertensive conditions.en
dc.typeArticleen
dc.identifier.doihttp://dx.doi.org/10.1111/bph.12203
dc.peerreviewedYesen
dc.researchinstituteInstitute for Allied Health Sciences Researchen


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