IMPAIRED ACTION OF LEVCROMAKALIM ON ATP-SENSITIVE K-ARTERY CELLS FROMSPONTANEOUSLY HYPERTENSIVE RATS( CHANNELS IN MESENTERIC)

The purpose of the present study was to test the hypothesis that prope rties of ATP-sensitive K+ channels are altered in arterial smooth musc le cells of hypertensive rats. Using a patch-clamp technique, we compa red effects of a K+ channel opener, leveromakalim, on membrane current s in mesenteric artery cells from adult Wistar Kyoto rats (WKY) and ag e-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-indepe ndent and a voltage-insensitive current in a dose-dependent manner in the whole-cell clamp configuration. The reversal potential of the evok ed current depended on extracellular K+ concentration. Application of 3 mu mol/L glibenclamide, a specific blocker of ATP-sensitive K+ chann els, abolished the levcromakalim-evoked current; however, the current was unaffected by either 1 mmol/L tetraethylammonium or 0.3 mu mol/L c harybdotoxin. These results suggest that the levcromakalim-evoked curr ent was carried through ATP-sensitive K+ channels. In SHR cells, the m aximal slope conductance of the levcromakalim-evoked current, normaliz ed by cell capacitance, was decreased, and the dose-response curve was shifted to the right compared with WKY cells. The levcromakalim actio n was not impaired in cells from hydralazine-treated SHR. In conclusio n, the action of levcromakalim on ATP-sensitive K+ channels in SHR mes enteric artery muscle cells was impaired compared with WKY cells. This impairment was corrected by long-term antihypertensive treatment.