Cardiovascular responses to retigabine in conscious rats - under normotensive and hypertensive conditions.
BACKGROUND 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.
Citation : Fretwell, L. and Woolard, J. (2013) Cardiovascular responses to retigabine in conscious rats - under normotensive and hypertensive conditions. British Journal of Pharmacology. online first
Research Institute : Institute for Allied Health Sciences Research
Peer Reviewed : Yes