Cardiovascular responses to retigabine in conscious rats--under normotensive and hypertensive conditions.

background and purposeRetigabine 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. 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 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. KEY

resultsUnder 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 AND IMPLICATIONS: 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.