Cerebral arteries from hypertensive rats failed to constrict to KV1 channel blockers and exhibited reduced KV1 current density and subunit expression compared to normotensive controls.
Does hypertension attenuate the dilator function of Shaker-type voltage-gated K+ (KV1) channels in cerebral arteries of rats?
Hypertension in rat models is associated with a loss of KV1 channel-mediated vasodilation in cerebral arteries due to a deficit of alpha(1.2)- and alpha(1.5)-subunits.
p-value: p=<0.05
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.
Tobin et al. (Sat,) conducted a other in Hypertension. Hypertension (genetic and renal models) vs. Normotensive control rats was evaluated on Reduction in resting diameter of pressurized cerebral arteries in response to KV1 channel block (correolide) (p=<0.05). Cerebral arteries from hypertensive rats failed to constrict to KV1 channel blockers and exhibited reduced KV1 current density and subunit expression compared to normotensive controls.