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The roles of, and interactions between, steroids and naloxone, an opioid antagonist, in the reversal of experimental hypotensive shock were studied in normal and adrenalectomized rats. In normal rats treated with dexamethasone or deoxycorticosterone or 17-hydroxyprogesterone the hypotension and shock caused by 1% bodyweight and 2% bodyweight haemorrhage could be substantially reversed by naloxone in a dose-related manner. In contrast, the reversal of hypotension by naloxone was markedly less in adrenalectomized rats. It is concluded that there is a co-ordinate release of pressor catecholamines and depressor enkephalins from adrenal glands in hypovolaemic shock. Eventually, the use of naloxone would be of much less value in the treatment of hypotension or shock in patients with Addison's disease.

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The effects of chronic thyroxine treatment on cat soleus muscle contractions were studied. Maximum twitch tension, contraction time, half relaxation time and tension-time integral of maximal twitches of the soleus muscles of thyroxine treated cats were significantly decreased. Consequently, there was a decrease in tension and degree of fusion of incomplete tetanic contractions of the soleus muscle. The maximum tetanic tension was not statistically significantly changed, suggesting that the effects may be due to a decrease in the duration of the active state of the muscle. Isoprenaline given intravenously during incomplete tetanic contractions of the soleus muscle caused a statistically significant depression of tension in the control group but not in the thyroxine treated group. This further suggests reduction in the duration of the active state of soleus muscles of thyroxine treated cats. Propranolol injected chronically with thyroxine reversed or prevented the depression of tension caused by thyroxine treatment, suggesting the involvement of beta-adrenoceptors in these effects. The decrease in tension and degree of fusion during incomplete tetanic contractions of the thyroxine treated soleus could be responsible, at least partly, for the muscle weakness and tremor of thyrotoxicosis. Cyclic AMP may possibly be the mediator of these effects.

1. The effects of thyroxine treatment on soleus and extensor digitorum longus (EDL) muscle contractions and their cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels were examined in anaesthetized cats. 2. Thyroxine treatment decreased the tension of incomplete tetanic contractions of the soleus as well as the EDL muscles. The effect on tension of these muscles was not associated with an increase in the cyclic AMP level of the muscle as is the case with a beta 2-adrenoceptor agonist effect. 3. The results do not support the involvement of cyclic AMP in the tension depressant effect of thyroxine on contractions of skeletal muscle. 4. It is suggested that the muscle weakness and tremor observed in thyrotoxicosis and during administration of beta 2-adrenoceptor agonists are mediated by different mechanisms.

1. Cyclic AMP levels have been determined in the soleus muscles of anaesthetized cats in the absence of drugs, and during depression of incomplete tetanic contractions produced by (-)-isoprenaline, ICI 63,197 (a phosphodiesterase inhibitor) or levodopa. 2. Cyclic AMP levels were elevated at the peak of tension depression produced by isoprenaline. Effects of isoprenaline on cyclic AMP and on contractions were dose dependent and statistically significantly related one to the other. Both effects were blocked by propranolol. 3. ICI 63,197 and levodopa produced isoprenaline-like effects on contractions but times to peak effect and recovery were longer. Cyclic AMP levels estimated during the depressant action were elevated. 4. The results support the involvement of cyclic AMP in the depressant effect of beta-adrenoreceptor agonists on slow-contracting mammalian skeletal muscle.

1Increasing the frequency of twitches and treatment with isoprenaline have been been compared for effects on twitch tension, tension-time integral and cyclic adenosine 3', 5'-monophosphate (cyclic AMP) levels in the slow-contracting soleus muscle of cats, anaesthetized with chloralose and pentobarbitone. The effect of change in frequency of contractions on cyclic AMP in the fastcontracting extensor digitorum longus muscle was also examined. 2 Although both isoprenaline and increasing the frequency of contractions depressed twitch tension in the soleus, only isoprenaline enhanced cyclic AMP levels. The effects of isoprenaline were independent of the existing frequency of contractions of the muscle. Increasing the frequency of contractions enhanced twitches in the extensor digitorum longus muscle but did not change cyclic AMP levels. 3 It is concluded that cyclic AMP may mediate effects of ,B-adrenoceptor agonists but not those caused by increasing the frequency of contractions on slow-or fast-contracting skeletal muscles.

1. Cyclic AMP and cyclic GMP levels were determined in bovine splenic nerve segments in the absence and presence of (+/-)-isoprenaline, (-)-phenylephrine, clonidine and ICI 63 197 (a phosphodiesterase inhibitor). The chosen concentrations of adrenoceptor agonists were those which are known to affect stimulation-induced overflow of noradrenaline from nerve terminals. 2. The mean levels of cyclic AMP ranged from 229 to 555 pmol/g of microwave irradiated tissue. Mean cyclic GMP levels ranged from 27.9 to 42.2 pmol/g. 3. Isoprenaline enhanced cyclic AMP levels but did not affect cyclic GMP levels. The effect was blocked with (+/-)-propranolol. ICI 63 197 increased cyclic AMP levels but did not change cyclic GMP. Phenylephrine and clonidine caused no consistent changes in cyclic AMP or cyclic GMP levels or in the concentration ratio between these two nucleotides. 4. The results support the involvement of cyclic AMP in the enhancing effect of beta-adrenoceptor agonists and phosphodiesterase inhibitors on stimulation-induced release of noradrenaline from sympathetic nerves.