This study tested whether activation of protein kinase A (PKA) & G (PKG) pathways would attenuate the ability of RhoA to suppress the delayed rectifier K⁺ (K_DR) current and limit agonist-induced depolarization and constriction. Smooth muscle cells from rat cerebral arteries were enzymatically isolated and whole cell K_DR currents monitored using conventional patch clamp electrophysiology. The K_DR current averaged 21.2 ± 2.3 pA/pF (mean ± SE) at +40 mV and was potently inhibited by uridine triphosphate (UTP). Current suppression was eliminated in the presence of C3 exoenzyme, confirming that this modulation is dependent on RhoA. Activation of PKA (dibutyryl cAMP; forskolin) or PKG (dibutyryl-cGMP; sodium nitroprusside; nitric oxide) similarly abolished the ability of UTP to suppress K_DR and did so without effect on baseline current. Using pressure myography techniques, cerebral arteries stripped of endothelium and pre-constricted with UTP were subsequently shown to hyperpolarize and dilate to both forskolin and SNP. An increase in K_V channel activity was found to partly underlie these associated changes as constriction to 4-aminopyridine (4-AP; K_DR channel blocker) was greater following PKA or PKG activation. We conclude from our electrophysiological and functional observations that the PKA and PKG pathways attenuate the ability of UTP to depolarize and constrict cerebral arteries in part by minimizing the RhoA-mediated suppression of the K_DR current.