Charybdotoxin‐sensitive K⁺ channels regulate the myogenic tone in the resting state of arteries from spontaneously hypertensive rats

Abstract

1 To determine the possible role of Ca2"-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 16Rb 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 10-7M nifedipine was added.3 The addition of charybdotoxin (ChTX, I0-'-I0-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 10-7 M 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.

ATP‐induced vasodilation in human skeletal muscle

“…Glibenclamide had no influence on the basal vascular tone of carotid, femoral, and mesenteric endothelium-denuded strips from rats (Asano et al, 1993). However, infusion of glibenclamide into the coronary vasculature of anesthetized dogs and in isolated rabbit hearts resultated in significant increase in coronary resistance.…”

Increased Ca2+ Buffering Function of Sarcoplasmic Reticulum in Small Mesenteric Arteries from Spontaneously Hypertensive Rats

“…Thus, it is likely that the alteration of the SR function in SHR is generally observed among the large arteries (the aorta and the carotid and femoral arteries) and the resistance artery (the small mesenteric artery). Because the expression of SR Ca 2 -ATPase (SERCA 2) gene is reportedly increased in the abdominal aorta and cultured aortic smooth muscle cells from SHR (9,16), because this abnormality is already detected in the femoral artery from 4-week-old SHR (31). Furthermore, the Ca 2 buffering function of the SR is increased in this artery (39).…”

Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells

“…The activation of BK Ca channels has been reported to control membrane potential and the degree of contraction and/or contractility in both vascular (Brayden and Nelson, 1992;Asano et al, 1993;Jaggar et al, 2000) and nonvascular (SuarezKurtz et al, 1991;Anwer et al, 1993) smooth muscle. Previous studies that showed bile acid-induced increases in K ϩ currents were performed in nonsmooth muscle preparations (Binah et al, 1987;Kotake et al, 1989;Devor et al, 1993).…”