Depression of Contractile Force of Skeletal Muscle by Intra-arterial Vasodilator Drugs

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Abstract
The intra-arterial administration of vasodilator drugs (acetylcholine, histamine, isoproterenol, adenosine triphosphate, bradykinin, and isoxsuprine hydrochloride) induced reversible depression in the maximal contractile force of the intermittently stimulated gastrocnemius-soleus muscles in the cat. In general, blood flow to the muscles was held constant and perfusion pressure was observed. The agents were effective in depressing the muscle at doses the same as those required to produce dilatation in the resting muscle. Increase in blood flow during infusion could reverse the depression. Atropine, in amounts sufficient to block the hypotensive action of intravenously administered acetylcholine, prevented the muscle depressant action of the latter, while leaving unaffected the action of histamine. Further experiments, utilizing mainly acetylcholine as the prototype, were performed to test the hypothesis that the depressant effect on the gastrocnemius was closely related to a vascular action of the drugs. Evidence serving both to exclude neuromuscular blockade and to support a vascular effect was adduced from three sets of observations. 1) In vitro tests of blocking action of acetylcholine and histamine on nerve-muscle preparations indicated that any such action would require doses several hundred times greater than those effective in the cat gastrocnemius. 2) Under conditions where dependency of contractile force on blood flow varied, comparison of the effects of acetylcholine to d -tubocurarine and decamethonium on the cat gastrocnemius showed that when dependency on flow was reduced the effect of acetylcholine was also, while neuromuscular blockade was affected little. 3) A decrease occurred in the I 131 clearance rate from the gastrocnemius parallel to the reduction in muscle force from acetylcholine, while a much smaller, or delayed, reduction in rate occurred when force was reduced equally by d -tuboeurarine. A redistribution of blood flow within the muscle and associated connective tissue may account for the results.