It is well known that vascular smooth muscle (SM) force development is closely coupled to membrane potential, which, in turn, is determined by potassium channels activity. The most important types of K+-channels family are: voltage-activated K+ channels (Kv), high conductance Ca2+-dependent potassium channels (BKCa), and ATP-sensitive K+ channels (KATP). Potassium conductance is altered in some pathological conditions such as essential (Cox et. al., 2001) and radiation-induced (Soloviev et. al., 2009) arterial hypertension. It is important that overproduction of reactive oxygen species (ROS) and high protein kinase C (PKC) activity are their own distinctive features. To determine a strategy for the relevant pharmacological interventions it is important to identify the most vulnerable targets. The goal of the study was to investigate the function and expression of BKCa, Kv, KATP in rat thoracic aorta SM from spontaneously hypertensive (SHR) and whole-body irradiated rats (IR). Irradiation was performed with gamma rays delivered at a rate of 0.8 Gy/min from a cobalt 60 source. The animals were killed 30 days after irradiation. Taking into account functional association between voltage-dependent calcium and K+ channels, L-type Ca2+ channels were studied additionally. Experimental design of the study comprised patch-clamp technique, RT-PCR analysis and standard Ach-test. BKCa component of outward current appears significantly decreased from control value of 48±5 pA/pF in healthy animals to 24±3 pA/pF and 14±2 pA/pF in SHR and IR, respectively (P<0.05, n=14) while the residual paxilline non-sensitive current was increased. The changes in BKCa activity in IR correlated with decreased levels of BKCa α- subunit mRNA in SM. In contrast, the mRNA level of other potassium channels and L-type Ca2+ channels was increased: Kv – from 0.025±0.004 to 0.10±0.016 (P<0.01, n=9) and KATP – from 0.22±0.04 to 0.72±0.07 relative units (P<0.01, n=9). The expression of gene encoding L-type Ca2+ channels was fourfold increased. The differences observed in gene expression in IR are tightly correlated with an increased Kv, KATP and Ca2+ channels activity. PKC inhibitor, chelerythrine (100 nM), restored BKCa activity and Ach-induced relaxation suppressed in SHR and IR. The RT-PCR analysis showed that PKC-δ isozyme mRNA expression is tenfold increased in SM from SHR and IR. The target-specific to PKC-δ small interfering RNA (siRNA) administration led to an increment in amplitude of Ach-induced relaxation and BKCa channels activity, and promoted arterial blood pressure normalization in SHR. In conclusion, BKCa channels appear to be the most ROS-sensitive among potassium channels family while Kv and KATP channels are resistant to oxidative stress and may constitute a reserve mechanism for the maintenance of tissue blood supply. It is likely that siRNA is a good approach to inactivate PKC gene encoding function and to normalize vascular tone damaged in SHR.