Charybdotoxin-sensitive K+ channels regulate the myogenic tone in the resting state of arteries from spontaneously hypertensive rats.
1. To determine the possible role of Ca(2+)-activated K+ (KCa) channels in the regulation of resting tone of arteries from spontaneously hypertensive rats (SHR), the effects of agents which interact with these channels on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid, femoral and mesenteric arteries from SHR and normotensive Wistar-Kyoto rats (WKY). 2. Strips of carotid, femoral and mesenteric arteries from SHR exhibited a myogenic tone; that is, the resting tone decreased when either the Krebs solution was changed to a 0-Ca2+ solution or 10(-7) M nifedipine was added. 3. The addition of charybdotoxin (ChTX, 10(-9)-10(-7) M), a blocker of large conductance KCa channels, to the resting strips of these arteries produced a concentration-dependent contraction, which was significantly greater in SHR than in WKY. Relatively low concentrations of tetraethylammonium (0.05-5 mM) produced a concentration-dependent contraction which was similar to the ChTX-induced contraction in these strips. 4. The ChTX-induced contractions in SHR were greatly attenuated by 10(-7) M nifedipine and by 3 x 10(-6) M cromakalim, a K+ channel opener. Cromakalim alone abolished the myogenic tone in SHR. 5. The addition of apamin (a blocker of small conductance KCa channels, up to 10(-6) M), or of glibenclamide (a blocker of ATP-sensitive K+ channels, up to 5 x 10(-6) M), to the resting strips failed to produce a contraction. 6. In resting strips of carotid, femoral and mesenteric arteries preloaded with 86Rb, the basal 86Rb efflux rate constants were significantly greater in SHR than in WKY. The addition of 10-7 M nifedipine to the resting strips decreased the basal 86Rb efflux rate constants only in SHR.7. The cellular Ca2+ uptake in the resting state of carotid and femoral arteries from SHR was significantly increased when compared to WKY, and this increase in SHR was significantly reduced by 10-7M nifedipine.8. These results suggest that the ChTX-sensitive KCa channels were highly activated to regulate the myogenic tone in the resting state of carotid, femoral and mesenteric arteries from SHR. The increased Kca channel functions in SHR arteries appeared to be secondary to the increased Ca2' influx via L-type voltage-dependent Ca2+ channels in the resting state of these arteries.
Asano
M
M
Department of Pharmacology, Nagoya City University Medical School, Japan.
Masuzawa-Ito
K
K
Matsuda
T
T
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D018999:Charybdotoxin; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012604:Scorpion Venoms / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015221:Potassium Channels; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D019789:Tetraethylammonium; D011188:Potassium; D002118:Calcium