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 withH-norepinephrine (H-NE), the drugs caused contraction and a progressive increase in overflow ofH-NE and O-methylated metabolites; 3,4-dihydroxyphenylglycol (DOPEG) decreased. Tissue uptake ofH-NE was partially inhibited. After surgical sympathectomy, both contraction andH-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 ofH-NE was unaffected by tetrodotoxin, but the later and larger overflow with prolonged exposure was depressed. The former occurred in the absence of Ca, but the latter was Cadependent. Inhibition of the neuronal amine carrier by cocaine or desipramine and blockade of the neuronal a-adrenoceptors with phentolamine or phenoxybenzamine attenuated the release ofH-NE evoked by ACS and ouabain. During electrical stimulation, ACS augmented the overflow ofH-NE. This was attenuated by cocaine, desipramine, and the a-adrenolytic drugs. ACS, like pargyline, augmented the overflow ofH-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 mono-amine oxidase activity, (3) facilitate and may trigger Ca-dependent exocytotic release of norepineph-rine, (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 a-adrenoceptors. Circ Res 47845-854, 1980