TY - JOUR
T1 - A ca2+-dependent k+ current is enhanced in arterial membranes of hypertensive rats
AU - Rusch, Nancy J.
AU - De Lucena, Roberto G.
AU - Wooldridge, Theresa A.
AU - England, Sarah K.
AU - Cowley, Allen W.
PY - 1992/4
Y1 - 1992/4
N2 - 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.
AB - 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.
KW - Blood pressure
KW - Calcium
KW - Ion channels
KW - Potassium
KW - Tetraethylammonium compounds
KW - Vascular smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=0026717465&partnerID=8YFLogxK
U2 - 10.1161/01.HYP.19.4.301
DO - 10.1161/01.HYP.19.4.301
M3 - Article
C2 - 1555863
AN - SCOPUS:0026717465
VL - 19
SP - 301
EP - 307
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 4
ER -