Anisodamine, which is originally extracted from scopolia tangutica and is 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 contraction of 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 vasodilation effect of some potassium channel 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 channel blockers inhibit anisodamine-induced relaxation of the rabbit isolated aortic rings. In a 8-min period, 1, 3 and 10 μmol/L of anisodamine, significantly relaxed the 0.01 umol/L NA precontracted aortic ring by (19.1±3.1)%, (30.1±3.8)% and (38.3±4.2)%, respectively, compared with the controls
(P<0.01). 10 mmol/L of CsCl (a non-selective potassium channel blocker), 1 mmol/L of 4-aminopyridine , 10 μmol/L BaCl2 (a selective inwardly-rectifying potassium channel blocker), 10 μmol/L of glibenclamide (a selective ATP-sensitive potassium channel blocker), 3 μmol/L of charybdotoxin (a large- and intermediate-conductance Ca2+-activated potassium channels blocker) and 3 μmol/L of 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 (P<0.01). In the presence of 10 and 30 mmol/L CsCl or 1 and 3 mmol/L 4-aminopyridine, anisodamine-induced relaxation of the 0.01 μmol/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-min period. However, in the presence of 10, 30 μmol/L of BaCl2, 10, 30 μmol/L of glibenclamide, 3 μmol/L of charybdotoxin, or 3 μmol/L apamin, 10 μmol/L anisodamine-induced relaxation <(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 decrease, 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.