Objective: 

It is known that protein kinase C (PKC) family plays an important role in hypertension development (Soloviev, Bershtein, 1992). The vascular smooth muscle (SM) tone is closely coupled to membrane potential, which, in turn, is determined by K⁺ channels activity. Potassium conductance is altered in both radiation-induced (Soloviev et al., 2009) and essential hypertension (Cox et al., 2001).

Methods: 

The goal of this study was to identify the most vulnerable target for pharmacological interventions in arterial hypertension. Experimental design of the study comprised patch-clamp technique, RT-PCR and standard ACh-test.

Results: 

We have measured the level of d-PKC gene expression in thoracic aorta from SHRs and SHRs treated with d-PKC siRNA relative to control rats. The RT-PCR analysis showed that PKC-d-isoform mRNA expression is sixfold increased in SMCs from SHRs and was significantly higher than seen in SHRs treated with d-PKC siRNA (control, 11.8±1.71, n=6; SHR, 43.61±6.32, n=6; SHRs treated with d-PKC siRNA, 33.76±1.28, n=6; p<0.05). BKCa component of outward current is significantly appears decreased from 48 ± 5 pA/pF in healthy rats to 25 ± 2 pA/pF in SHRs while in SHRs treated with d-PKC siRNA it was 35 ± 3 pA/pF, P<0.05, n=18. The target-specific to d-PKC siRNA administration led to an increment in amplitude of ACh-relaxation and BKCa activity, and promoted arterial blood pressure normalization in SHRs.

Conclusions: 

In conclusion, d-PKC gene silencing restores endothelium-dependent relaxation and BKCa channels function in vascular SHR SM cells. It is likely that siRNA is a good approach to inactivate PKC gene encoding function and to normalize vasodilator potential in SHRs.