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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/1/H293    most recent 00991.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tobin, A. A. Articles by Rhee, S. W. PubMed PubMed Citation Articles by Tobin, A. A. Articles by Rhee, S. W.

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

¹Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin; ²Department of Physiology, College of Medicine, Sultan Qaboos University, Al-khod, Sultanate of Oman; ³Department of Neurology, Medical College of Wisconsin and Clement J. Zablocki Department of Veterans Affairs Medical Center, Milwaukee, Wisconsin; and ⁴Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas

Submitted 11 September 2008 ; accepted in final form 24 April 2009

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 _1.2- and _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 -subunits. Collectively, these findings demonstrate that a deficit of _1.2- and _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.

potassium channels; vascular smooth muscle; cerebral arteries; hypertension