Inward rectifier (K_IR) and ATP-sensitive (K_ATP) K⁺ channels play essential roles in vascular smooth muscle cells (VSMCs) as they contribute to maintain the resting membrane potential (E_M) and in this way regulate the contractile tone of resistance arteries. K_ATP channels underscore the functional bond between cellular metabolism and membrane excitability, and their blockade results in vasoconstriction and depolarization in various types of VSM. K_IR channels are known to be abundant in the VSMCs of resistance vessels, where their roles are far from being completely understood, although it has been established that they contribute to the resting E_M and resting tone of these cells and that their activation in response to moderate increases in extracellular K⁺ induces vasodilation. We designed this study to examine the expression and function of these channels in VSM and their regulation in essential hypertension, using VSMCs from mesenteric arteries obtained from a hypertensive inbred mice strain, BPH, and the corresponding normotensive strain, BPN. All animal protocols were approved by the Institutional Care and Use Committee of our Institution. Mice were killed by decapitation after isofluorane anesthesia. Real-time PCR using low-density TaqMan® arrays reveals mRNA expression of several K_IR and K_ATP genes in mesenteric VSMCs and also shows a reduced expression of some of these genes under hypertensive conditions. Functional characterization of K_IR and K_ATP channels was performed in freshly dispersed VSMCs with the whole-cell configuration of the patch-clamp technique, using BaCl₂ (100 μM) to block K_IR channels and pinacidil (10 μM) to activate K_ATP channels. Pinacidil application induced an increase of the current amplitude that was larger in BPN than in BPH VSMCs. We also found a decrease in the amplitude of the BaCl₂-sensitive current in VSMCs from BPH mice. The contribution of K_IR channels to the resting E_M was evaluated in perforated-patch experiments, where we observed a significant reduction of the BaCl₂-induced depolarization in hypertensive VSMCs. Finally, the contribution of K_IR and K_ATP channels to determine vascular tone in mesenteric arteries of BPN and BPH mice was explored in pressurized arteries. Altogether, our findings indicate that the observed decrease in the functional expression of K_IR and K_ATP channels in BPH VSMCs from resistance arteries could participate in the genesis of the altered vascular tone during hypertension.