Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries

Abstract

1 The hypotensive and vasorelaxant e ect of dioclein in resistance mesenteric arteries was studied in intact animals and isolated vessels, respectively. 2 In intact animals, initial bolus administration of dioclein (2.5 mg kg 71 ) produced transient hypotension accompanied by an increase in heart rate. Subsequent doses of dioclein (5 and 10 mg kg 71 ) produced hypotensive responses with no signi®cant change in heart rate. N G -nitro-Larginine methyl ester (L-NAME) did not a ect the hypotensive response. 3 In endothelium-containing or -denuded vessels pre-contracted with phenylephrine, dioclein (5 and 10 mg kg 71 produced a concentration-dependent vasorelaxation (IC 50 =0.3+0.06 and 1.6+0.6 mM, respectively) which was not changed by 10 mM indomethacin. L-NAME (300 mM) produced a shift to the right. 4 Dioclein was without e ect on contraction of vessels induced by physiological salt solution (PSS) containing 50 mM KCl and the concentration dependence of dioclein's e ect on phenylephrine induced contraction was shifted to the right in vessels bathed in PSS containing 25 mM KCl. 5 Tetraethylammonium (10 mM) and BaCl 2 (1 mM) increased the IC 50 for dioclein-induced vasorelaxation without a ecting the maximal response (E max ). Charybdotoxin (100 nM), 4-aminopyridine (1 mM) and iberiotoxin (100 nM) increased the IC 50 and reduced the E max . Apamin (1 mM) reduced the E max without a ecting the IC 50 . 6 Dioclein produced a hyperpolarization in smooth muscle of mesenteric arteries with or without endothelium (7.7+1.4 mV and 12.3+3.6 mV, respectively). 7 In conclusion dioclein lowered arterial pressure probably through a decrease in peripheral vascular resistance. The underling mechanism implicated in the vasorelaxant e ect of dioclein appears to be the opening of K Ca and Kv channels and subsequent membrane hyperpolarization.

Cardiovascular Ion Channels as a Molecular Target of Flavonoids

“…Similar effects have been shown for the isoflavone puerarin [32]. Dioclein, a flavonoid isolated from the root of Dioclea grandiflora, a legume of the native Americans, causes hypotension in normotensive rats [33]. Using preparations of isolated rat mesenteric arteries, the authors showed that the vasorelaxant effect is mainly due to hyperpolarization caused by an opening of BK Ca channels [33].…”

“…Dioclein, a flavonoid isolated from the root of Dioclea grandiflora, a legume of the native Americans, causes hypotension in normotensive rats [33]. Using preparations of isolated rat mesenteric arteries, the authors showed that the vasorelaxant effect is mainly due to hyperpolarization caused by an opening of BK Ca channels [33]. Saponara et al found that the citrus flavonoid naringenin also dilates endothelium denuded rat aortic rings by activation of BK Ca channels [34].…”

Hypotensive and endothelium-independent vasorelaxant effects of methanolic extract from Curcuma longa L. in rats

“…To investigate the possible mechanism(s) responsible for CLME-induced relaxation, the preparations without endothelium were pre-contracted with phenylephrine (10 M) for 30 min after being pre-incubated with one of the following inhibitors: glibenclamide (10 M), BaCl 2 (1 mM), tetraethylammonium (1 mM) or 4-aminopyridine (1 mM). The concentration used for each inhibitor of K + channels is sufficient to antagonize selectively those channels in arterial smooth muscle (Nelson and Quayle, 1995;Côrtes et al, 2001).…”

Mechanisms Underlying the Vasorelaxant Effect Induced by Proanthocyanidin-Rich Fraction From Croton celtidifolius in Rat Small Resistance Arteries

“…In this case, the relaxation in response to exogenous NO is resistant to inhibitors of guanylate cyclase. This additional component of relaxation has been named endothelium-derived hyperpolarizing factor (EDHF) (17,22). The contribution of NO and EDHF to endotheliumdependent vasodilation varies according to the vessel studied (27).…”

“…Superior MAs were isolated as described previously by Cortês and colleagues (17). In brief, rats were killed by exposure to CO 2 and exsanguinated.…”