We examined the effects of acute hypoxia on Ba²⁺-sensitive inwardly rectifying K⁺ (Kir) current in coronary arterial smooth muscle cells from humanely killed rabbits. The amplitudes of Kir current was definitely higher in the cells from small-diameter (o.d. 200 μm, LCASMC, -1.5± 0.1 pA/pF). Western blot analysis confirmed that Kir2.1 protein was expressed in SCASMC but not in LCASMC. The hypoxic condition was attained by perfusing the bath with normal Tyrode solution bubbled with 100% N₂. In SCASMC, the Kir current was significantly increased by the hypoxic stimulation. This effect was blocked by the adenylyl cyclase inhibitor SQ 22536 (10 μM) and mimicked by forskolin (10 μM) and dibutyryl-cAMP (500 μM). The production of cAMP in SCASMC was measured by ELISA, which increased 5.7-fold following 6 min of hypoxia. Hypoxia-induced increase in Kir currents was abolished by the protein kinase A (PKA) inhibitors Rp-8-CPT-cAMPs (10 μM) and KT 5720 (1 μM). The inhibition of G-protein with GDPβs (1 mM) partially reduced (~50%) the hypoxia-induced increase in Kir currents. In Langendorff-perfused rabbit hearts, hypoxia increased coronary blood flow, an effect that was inhibited by Ba²⁺. In summary, the hypoxia augments the Kir currents in SCASMC via cAMP and protein kinase A-dependent signalling cascades, which might, at least partly, explain the hypoxia-induced coronary vasodilatation.