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(V)1) channels is attenuated in middle cerebral arteries from two rat models of hypertension. Block of K(V)1 channels by correolide (1 micromol/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 Ca(2+)-dependent tone and failed to significantly constrict to correolide or psora-4, implying a loss of K(V)1 channel-mediated vasodilation. Patch-clamp studies in the VSMCs of SHR confirmed that the peak K(+) current density attributed to K(V)1 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 alpha(1.2)- and alpha(1.5)-subunits that compose K(V)1 channels in cerebral arteries of SHR and Ao-B rats compared with control animals. In each case, the deficiency of K(V)1 channels was associated with reduced mRNA levels encoding either or both alpha-subunits. Collectively, these findings demonstrate that a deficit of alpha(1.2)- and alpha(1.5)-subunits results in a reduced contribution of K(V)1 channels to the resting diameters of cerebral arteries from two rat models of hypertension that originate from different etiologies.
Pubmed ID: 19411284 RIS Download
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