The effects of acetylstrophanthidin and ouabain on the sympathetic adrenergic neuroeffector junction in canine vascular smooth muscle.
We performed experiments to determine the effects of acetylstrophanthidin (ACS) and ouabain on the adrenergic neuroeffector junction in dog saphenous veins. In quiescent strips incubated with 3H-norepinephrine (3H-NE), the drugs caused contraction and a progressive increase in overflow of 3H-NE and O-methylated metabolites; 3,4-dihydroxyphenylglycol (DOPEG) decreased. Tissue uptake of 3H-NE was partially inhibited. After surgical sympathectomy, both contraction and 3H-NE overflow were markedly attenuated. Following chemical sympathectomy with 6-hydroxydopamine, ouabain contractions were 11% of control, whereas the contractions due to exogenous norepinephrine were exaggerated. The initial overflow of 3H-NE was unaffected by tetrodotoxin, but the later and larger overflow with prolonged exposure was depressed. The former occurred in the absence of Ca2+, but the latter was Ca2+ dependent. Inhibition of the neuronal amine carrier by cocaine or desipramine and blockade of the neuronal alpha-adrenoceptors with phentolamine or phenoxybenzamine attenuated the release of 3H-NE evoked by ACS and ouabain. During electrical stimulation, ACS augmented the overflow of 3H-NE. This was attenuated by cocaine, desipramine, and the alpha-adrenolytic drugs. ACS, like pargyline, augmented the overflow of 3H-NE evoked by tyramine and depressed that of DOPEG. These experiments suggest that acetylstrophanthidin and ouabain (1) cause contraction of vascular smooth muscle by displacement of norepinephrine from neuronal stores, (2) reduce neuronal monoamine oxidase activity, (3) facilitate and may trigger Ca2+-dependent exocytotic release of norepinephrine, (4) partially inhibit the neuronal amine carrier mechanism but do not interfere with extraneuronal disposition of norepinephrine, and, finally (5) may have unexplained interactions with prejunctional alpha-adrenoceptors.
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D009131:Muscle, Smooth, Vascular; D009451:Neuroeffector Junction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects; D013327:Strophanthidin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D011941:Receptors, Adrenergic; D010042:Ouabain; D013327:Strophanthidin; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine