Abstract
The mechanism underlying the relaxant response of rat aortic rings to the diterpene jatrophone was investigated. Jatrophone (3 and 10 μM) did not affect acetylcholine-induced endothelium-dependent relaxations, but caused concentration-dependent inhibition of noradrenaline (NA)-induced concentrations in unrubbed, and to a lesser extent, in denuded rings. Jatrophone (30 μM) fully prevented responses to angiotensin II and NA, while responses to KCl (up to 220 mM) were unaffected. In depolarizing medium (KCl 40 mM), jatrophone (3–30 μM) anatagonized Ca 2+-induced contractions in a concentration-dependent and noncompetitive manner, while verapamil (10–100 nM) caused a concentration-dependent, rightward displacement and depression of the Ca 2+ concentration-response curve. Jatrophone (1 to 300 μM) concentration dependently relaxed rat aortic rings precontraction with either NA (1 μM) of KCl (80 mM), yielding EC 50 s of 11 and 24 μM, respectively. These relaxant responses to jatrophone were unaffected by glibenclamide (1 μM), but the concentration-response curve was displaced to the right (2- to 8-fold) by other K + channel blockers such as tetraethylammonium (10 and 30 mM), 4-aminopyridine (3 and 10 mM) or procaine (1 and 3 mM). These results indicate that jatrophone relaxes the rat aorta, at least in part, by activating K + channels distinct from the ATP-sensitive subtype. Since jatrophone, like verapamil, relaxed preparations contracted with KCl and inhibited Ca 2+-induced contractions in depolarized preparations, this diterpene may also block Ca 2+ influx through voltage-sensitive channels. However, additional actions of jatrophone on receptor-operated Ca 2+ channels causing Ca 2+ efflux and/or release cannot be fully ruled out.
Published Version
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