Issue Archive

Voltage-activated potassium channel blockers inhibit anisodamine-induced relaxation of rabbit aortic smooth muscles precontracted with noradrenaline

Liu Shuqin, Zang Weijin, Li Zengli, Sun Qiang, Yu Xiaojiang, Luo Hongli, Zhu Shuming

Department of Pharmacology, School of Medicine, Xi'an Jiaotong University.Xi'an 710061,Shaanxi

Abstract

Anisodamine, which originally extracted from scopolia tangutica and currently produced in China, is a tropane alkaloid and a muscarinic cholinoceptor blocker. Our previous study found that anisodamine did not alter high K+-evoked contractions in rabbit aortic rings using isometric tension recording methods, but could attenuate noradrenaline (NA), histamine or 5-hydroxytryptamine-induced contraction in an endothelium-independent manner. Since the high K+-elicited depolarization non-selectively inhibits potassium channels in vascular smooth muscle cell (VSMC) membrane, the vasodilator action of some potassium channels activators may be inhibited or abolished in high K+ solution. We hypothesized that some potassium channels in VSMC membrane might play a role in the anisodamine-induced relaxation of blood vessels. The present experiment was designed to investigate whether potassium channels blockers inhibit anisodamine-induced relaxation of the rabbit isolated aortic ring. In a 8-minute period, anisodamine, 1, 3 and 10 #mu#mol/L, significantly relaxed the 0.01 #mu#mol/L NA precontracted aortic ring (by 19.1 ± 3.1 %, 30.1 ± 3.8 % and 38.3 ± 4.2 %, respectively) compared with the controls (by 4.8 ± 2.4 %, 5.1 ± 1.8 % and 5.6 ± 2.5 %, respectively) (P<0.01). 10 mmol/L CsCl (a non-selective potassium channel blocker), 1 mmol/L 4-aminopyridine (a selective voltage-activated potassium channel (KV) blocker), 10 #mu#mol/L BaCl_(2) (a selective inwardly-rectifying potassium channel blocker), 10 #mu#mol/L glibenclamide (a selective ATP-sensitive potassium channel blocker), 3 #mu#mol/L charybdotoxin (a large- and intermediate- conductance Ca2+-activated potassium channels blocker) and 3 #mu#mol/L apamin (a selective small conductance Ca2+-activated potassium channel blocker) significantly increased the NA–induced contraction by 14.4 ± 3.2 %, 16.3 ± 5.8 %, 12.7 ± 4.2 %, 13.6 ± 2.0 %, 11.1 ± 5.5 % and 13.4 ± 4.3 % respectively compared with the control ( by 5.6 ± 1.2 %) (P<0.01). In the presence of 10 and 30 mmol/L CsCl or 1 and 3 mmol/L 4-aminopyridine, anisodamine-induced relaxations of the 0.01 #mu#mol/L NA contracted rabbit aortic rings (28.8 ± 3.0 % and 15.9 ± 3.7 % or 29.7 ± 3.9 % and 19.0 ± 5.0 %) significantly deceased compared with that in the absence of any potassium channel blocker (38.3 ± 4.2 % ) (P<0.01) in a 8-minute period. However, in the presence of 10, 30 #mu#mol/L BaCl_(2), 10, 30 #mu#mol/L glibenclamide, 3 #mu#mol/L charybdotoxin, or 3 #mu#mol/L apamin, 10 #mu#mol/L anisodamine-induced relaxations (37.1 ± 3.8 %, 36.2 ± 4.7 %, 36.1 ± 2.7 %, 35.6 ± 3.3 %, 37.8 ± 2.0 % and 39.3 ± 4.7 %, respectively) did not deceased compared with the control (38.3 ± 4.2 % ) (P>0.05). This study suggests that KV blockers inhibit anisodamine-induced relaxation of the rabbit aortic smooth muscle precontracted with NA and implies that the KV in VSMC membrane plays a role in anisodamine-induced relaxation of blood vessels.

Key words: Potassium channel;Voltage-activated potassium channel;Anisodamine;Rabbit;aorta;Noradrenaline

Received: 　　Accepted:

Corresponding author: 　　E-mail:

Citing This Article：

Liu Shuqin, Zang Weijin, Li Zengli, Sun Qiang, Yu Xiaojiang, Luo Hongli, Zhu Shuming. Voltage-activated potassium channel blockers inhibit anisodamine-induced relaxation of rabbit aortic smooth muscles precontracted with noradrenaline. Acta Physiol Sin 2005; 57 (1): (in Chinese with English abstract).