1. The effects of 4-aminopyridine on the contractility of the fast-contracting tibialis anterior and the slow-contracting soleus muscles of cats under chloralose anaesthesia have been studied. 2. 4-Aminopyridine, in doses of 0.5 mg/kg and above, produced a slowly developing increase in the twitch tension of directly stimulated chronically denervated and of indirectly stimulated innervated tibialis anterior muscles, but had little or no effect on twitches of soleus muscles. The effect of innervated tibialis anterior muscles was more pronounced than that on chronically denervated muscles, but it was nevertheless concluded that the whole effect on innervated muscles was the result of a direct action on the muscle fibres. The simultaneously occurring facilitatory action on neuromuscular transmission, which is manifested in the anti-curare action of 4-aminopyridine, had a faster time-course and occurred in both the tibialis anterior and the soleus muscles. 3. 4-Aminopyridine antagonized dantrolene sodium on on the tibialis anterior muscle but not on the soleus muscle. The antagonism could be described as physiological antagonism since it simply reflected the opposing actions on contractility of the two drugs. 4. 4-Aminopyridine was without effect on maximal tetanic tension of either the tibialis anterior or the soleus muscle. 5. It seems clear from the literature that a species difference exists with regard to the ability of 4-aminopyridine to increase muscle contractility. The results described in this paper show that muscle differences within the same species also exist.

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Acute ethanol exposure depresses cardiac electromechanical function, whereas chronic ethanol consumption leads to the development of a specific myopathic state. Chronic hypertension and aging have similar effects in the impairment of myocardial function. However, little is known about the effects of ethanol on cardiac mechanical function in hypertension. We studied the effect of age on baseline mechanical properties and the inotropic response to clinically relevant concentrations of ethanol (18 to 71 mmol/L) using papillary muscles from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 10 and 25 weeks of age. Mechanical parameters measured were peak tension developed, time to peak tension, time to 90% relaxation, and maximal velocities of tension development and tension decline. SHR exhibited elevated systolic pressure and body weight as well as cardiomegaly and hepatomegaly at 10 and 25 weeks of age. Baseline mechanical properties were similar in SHR and WKY muscles at 10 weeks, whereas at 25 weeks, SHR muscles developed less tension, and both maximal velocities of tension development and tension decline were markedly depressed. Ethanol exposure produced concentration-dependent negative inotropic effects in both groups at both ages. Ethanol (> 18 nmol/L) decreased peak tension developed in both groups at 10 weeks, although higher concentrations were required at 25 weeks. The negative inotropic effect of ethanol resulted in the shortening of time to 90% relaxation in both groups at 10 weeks and was associated with a slowing of maximal velocities of both tension development and tension decline. The results suggest that aging depresses baseline mechanical properties when coupled with hypertension. In addition, the magnitude of the negative inotropic effect of ethanol was attenuated in both groups at 25 weeks of age.

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