Loss of cerebrovascular Shaker-type K⁺ channels: A shared vasodilator defect of genetic and renal hypertensive rats

The cerebral arteries of hypertensive rats are depolarized and highly myogenic, suggesting a loss of K⁺ channels in the vascular smooth muscle cells (VSMCs). The present study evaluated whether the dilator function of the prominent Shaker-type voltage-gated K⁺ (K_V1) channels is attenuated in middle cerebral arteries from two rat models of hypertension. Block of K_V1 channels by correolide (1 μmol/l) or psora-4 (100 nmol/l) reduced the resting diameter of pressurized (80 mmHg) cerebral arteries from normotensive rats by an average of 28 ± 3% or 26 ± 3%, respectively. In contrast, arteries from spontaneously hypertensive rats (SHR) and aortic-banded (Ao-B) rats with chronic hypertension showed enhanced Ca²⁺-dependent tone and failed to significantly constrict to correolide or psora-4, implying a loss of K_V1 channel-mediated vasodilation. Patch-clamp studies in the VSMCs of SHR confirmed that the peak K⁺ current density attributed to K_V1 channels averaged only 5.47 ± 1.03 pA/pF, compared with 9.58 ± 0.82 pA/pF in VSMCs of control Wistar-Kyoto rats. Subsequently, Western blots revealed a 49 ± 7% to 66 ± 7% loss of the pore-forming α_1.2- and α_1.5-subunits that compose K_V1 channels in cerebral arteries of SHR and Ao-B rats compared with control animals. In each case, the deficiency of K_V1 channels was associated with reduced mRNA levels encoding either or both α-subunits. Collectively, these findings demonstrate that a deficit of α_1.2- and α_1.5- subunits results in a reduced contribution of K_V1 channels to the resting diameters of cerebral arteries from two rat models of hypertension that originate from different etiologies.