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Hypertension. 1996;27:1234-1239

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(Hypertension. 1996;27:1234-1239.)
© 1996 American Heart Association, Inc.


Articles

Impaired Action of Levcromakalim on ATP-Sensitive K+ Channels in Mesenteric Artery Cells From Spontaneously Hypertensive Rats

Yusuke Ohya; Motoko Setoguchi; Koji Fujii; Tetsuhiko Nagao; Isao Abe; Masatoshi Fujishima

From the Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

Correspondence to Yusuke Ohya, MD, PhD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-82, Japan. E-mail ohya@intmed2.med.kyushu-u.ac.jp.

Abstract The purpose of the present study was to test the hypothesis that properties of ATP-sensitive K+ channels are altered in arterial smooth muscle cells of hypertensive rats. Using a patch-clamp technique, we compared effects of a K+ channel opener, levcromakalim, on membrane currents in mesenteric artery cells from adult Wistar Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR) treated or not treated with hydralazine. Blood pressure was significantly higher in SHR than in WKY or hydralazine-treated SHR. Levcromakalim evoked a time-independent and voltage-insensitive current in a dose-dependent manner in the whole-cell clamp configuration. The reversal potential of the evoked current depended on extracellular K+ concentration. Application of 3 µmol/L glibenclamide, a specific blocker of ATP-sensitive K+ channels, abolished the levcromakalim-evoked current; however, the current was unaffected by either 1 mmol/L tetraethylammonium or 0.3 µmol/L charybdotoxin. These results suggest that the levcromakalim-evoked current was carried through ATP-sensitive K+ channels. In SHR cells, the maximal slope conductance of the levcromakalim-evoked current, normalized by cell capacitance, was decreased, and the dose-response curve was shifted to the right compared with WKY cells. The levcromakalim action was not impaired in cells from hydralazine-treated SHR. In conclusion, the action of levcromakalim on ATP-sensitive K+ channels in SHR mesenteric artery muscle cells was impaired compared with WKY cells. This impairment was corrected by long-term antihypertensive treatment.


Key Words: rats, inbred, SHR • patch clamp techniques • potassium channels • hydralazine • adenosine triphosphate




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