The influence of histamine and other vasoactive substances on contractile responses of cat skeletal muscle to acetylcholine.

1. The effect of vasoactive substances, chiefly histamine, on contractions of cat skeletal muscle evoked by acetylcholine has been studied. For this purpose all of these agents were administered intra-arterially to anterior tibialis, chiefly, and also to soleus and external rectus muscles in vivo.2. Under these conditions, histamine itself never altered the resting tension of the muscle, but always enhanced the increase in tension produced by acetylcholine injected shortly afterward.3. On the anterior tibialis muscle, it was determined that the threshold potentiating dose of histamine was 0.001 mug/kg, and that maximal enhancement occurred when 0.1 mug/kg was injected 15 s before fixed, submaximal doses of acetylcholine. Injected 15 s before graded doses of acetylcholine, histamine 0.1 mug/kg shifted the acetylcholine dose-response curves approximately 1.5 log units to the left.4. Under similar experimental conditions the vasodilator, bradykinin, 0.001-1 mug/kg, and procedures which produce a local increase in nutritive capillary blood flow also enhanced acetylcholine-evoked contractile responses of the anterior tibialis, whereas the vasoconstrictor, angiotensin, 0.001-1 mug/kg, inhibited them.5. The potentiating effect of histamine was antagonized by mepyramine, but was undiminished by denervation of the muscle either acutely or for 4 days.6. Histamine failed to enhance responses of the muscle to electrical stimulation of either the muscle, directly, or its motor nerve.7. Histamine also had no effect upon acetylcholine-evoked responses of the isolated external rectus muscle in vitro.8. It is suggested that the potentiating effect of histamine in vivo is due to its vasodilator action within the muscles which, by relaxing arterioles and precapillary sphincters, could allow more of the blood-borne acetylcholine to reach more of its receptors on the muscle fibres in a given time.