| Autor: |
Tobin, A. A., Jose, B. K., Al-Kindi, H. N., Albarwani, S., Madden, J. A., Nemetz, L. T., Rusch, N. J., Rhee, S. W. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Jul2009, Vol. 297 Issue 1, p293-303, 11p, 11 Graphs |
| Abstrakt: |
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+ (Kv1) channels is attenuated in middle cerebral arteries from two rat models of hypertension. Block of Kv1 channels by correolide (1 μmol/1) or psora-4 (100 nmol/1) 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 Kv1 channel-mediated vasodilation. Patch-clamp studies in the VSMCs of SHR confirmed that the peak K+ current density attributed to Kv1 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 poreforming α1,2- and α1,5-subunits that compose Kv1 channels in cerebral arteries of SHR and Ao-B rats compared with control animals. In each case, the deficiency of Kv1 channels was associated with reduced mRNA levels encoding either or both a-subunits. Collectively, these findings demonstrate that a deficit of α1,2- and α1,5-subunits results in a reduced contribution of Kv1 channels to the resting diameters of cerebral arteries from two rat models of hypertension that originate from different etiologies. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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