Essential hypertension involves a gradual and sustained increase in total peripheral resistance, reflecting an increased vascular tone. Changes in the expression profile of voltage-dependent ion channels that promote arterial contraction have been postulated to participate in the development of hypertension. However, the changes in the expression and/or modulation of voltage-dependent K⁺ channels (Kv channels), are poorly defined, due to their large molecular diversity and their vascular bed-specific profile. We have studied the molecular and functional characterization of Kv channels in vascular smooth muscle (VSMCs) and their regulation in essential hypertension, using VSMCs from resistance (mesenteric) or conduit (aortic) arteries obtained from a hypertensive inbred mice strain, BPH, and the corresponding normotensive strain, BPN. Real-time PCR using low-density taqman® arrays reveals arterial bed-specific changes under hypertensive conditions. To study their functional relevance, we have characterize the electrophysiological properties of mesenteric VSMCs from BPN and BPH mice. VSMCs from BPH mesenteric arteries were more depolarized that BPN ones, showed significantly larger capacitance values, and reduced total Kv current density. Application of 50 nM stromatoxin inhibited 34% of the Kv current at +40 mV in BPN cells, but only 21% in BPH cells, suggesting a reduction in the functional expression of Kv2 channels in BPH VSMCs. These findings agree with the "de novo" expression of Kv6.3 mRNA in BPH mesenteric VSMCs, as Kv6.3 subunits associate with Kv2 channels to form heteromultimers with decreased current amplitude. Supported by ISCIII grants R006/009 (Red Heracles) and PI041044, MEC grant BFU2004-05551 and JCyL grant VA011C05