A ca²⁺-dependent k⁺ current is enhanced in arterial membranes of hypertensive rats

This study was designed to investigate the role and regulation of arterial membrane K⁺ channels in hypertension. Aortic segments from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were suspended for isometric tension recording. In other experiments, proximal aortic segments (PS) (exposed to high pressure) and distal aortic segments (DS) (exposed to lower pressure) were removed from surgically coarcted Sprague-Dawley rats and similarly prepared. Aortas from SHR and PS dose-dependently contracted to the K⁺ channel blocker tetraethylammonium (TEA) (0.1-10 mM), and this contraction was abolished by preincubation with 0.1 μM nifedipine. In contrast, the same concentrations of TEA did not contract either WKY or DS aortas. Since block of K⁺ channels by TEA had a different effect on aortic segments exposed to high versus low blood pressure, we compared whole-cell K⁺ currents in isolated vascular cells from the same aortas. The reversal potentials of depolarization- induced outward currents in WKY, SHR, DS, and PS aortic cells showed a Nemst relation to external K⁺ concentration indicative of selective K⁺ permeability. TEA (1 and 10 mM) was equipotent in blocking these K⁺ currents in patch-clamped cells from all aortic preparations, suggesting that the lack of TEA-induced contractions in WKY and DS aortas was not due to an absence of TEA-sensitive K⁺ channels in these arterial membranes. However, when the Ca²⁺ ionophore A23187 (10 μM) was used to increase the level of cytosolic Ca²⁺ in patch-clamped cells, the K⁺ current density in SHR and PS aortic cells was twofold or more higher than in WKY and DS cells. These data suggest that a Ca²⁺-activated, TEA-sensitive K⁺ current is enhanced in aortic muscle cells exposed to high blood pressure. In the intact blood vessel, this may act as a compensatory mechanism to modulate the level of arterial contraction in hypertension.