Neurally Mediated and Direct Effects of Acetylstrophanthidin on Canine Skeletal Muscle Vascular Resistance

The effects of acetylstrophanthidin on the vascular resistance of the isolated canine gracilis muscle were examined in 38 anesthetized mongrel dogs. The neurally mediated effect of intravenous acetylstrophanthidin (0.5 mg) on the vascular resistance of the innervated, separately perfused (constant flow) right gracilis muscle was a transient mean fall of 4.0 ± 0.9 resistance units (RU) ( P < 0.001) at 1 minute followed by a sustained rise to 4 RU (P < 0.05) above control from 8 to 18 minutes after injection. The sustained increase in resistance was blocked by intra-arterial phenoxybenzamine. The combined direct and neurally mediated effects of intravenous acetylstrophanthidin were directionally similar and greater in magnitude in the innervated, autoperfused (intact circulation) left gracilis. Following denervation of the muscle, however, the initial decrease in vascular resistance was abolished and the prolonged subsequent rise was greatly reduced. Hence the initial fall and most of the subsequent rise in vascular resistance are neurally mediated. There was no consistent change in aortic pressure to explain either of these changes in vascular resistance solely on a reflex basis. Thus, systemically administered acetylstrophanthidin produces skeletal muscle vasoconstriction through both a direct and a neurally mediated effect. The latter is mediated through alpha-receptor stimulation and appears to be the predominant mechanism whereby this drug increases muscle vascular resistance. KEY WORDS digitalis alpha receptors muscle exercise denervation of the carotid bifurcations vagotomy • Digitalis has been considered to have both a direct and a neurogenic effect on peripheral vascular resistance. The direct vasoconstrictor effect of digitalis on vascular smooth muscle is well established (1). However, controversy exists as to whether the principal neurogenic effect of digitalis is withdrawal or enhance-ment of sympathetic tone mediated by alpha-receptors. Ross et al. (1), Mason an