Impaired action of levcromakalim on ATP-sensitive K+ channels in mesenteric artery cells from spontaneously hypertensive rats.
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, levromakalim, 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 micromol/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 micromol/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.
Ohya
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Setoguchi
M
M
Fujii
K
K
Nagao
T
T
Abe
I
I
Fujishima
M
M
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D010276:Parasympatholytics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D011674:Pulse / Q000187:drug effects; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D001578:Benzopyrans; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D006830:Hydralazine; D005905:Glyburide