The load sensitivity of the relaxation phase was studied in rat papillary muscle, with isotonic afterloaded contractions and stretches applied after the peak of isometric twitches. The tension decay occurred earlier in isotonic than in isometric contractions. When a central region of the preparation was marked with small stainless steel pins, a lengthening of this region could be shown during relaxation of isometric (fixed end) contractions. This lengthening was earlier and faster in isotonic afterloaded contractions. Therefore the sensitivity of relaxation to load or length changes could be described in the context of the general mechanism of relaxation which takes into account the non uniform behaviour of the muscle and the internal movement during contractions. Interventions which decelerate the activation decay rate had different effects on the load dependence of relaxation. Caffeine addition and substitution of strontium for calcium abolished the load sensitivity while a temperature reduction had no influence on it.

Isolated atrial and ventricular preparations from rat heart have been compared. In atrial specimens relaxation is faster than in papillary muscles both in isometric and isotonic conditions. In papillary muscles the tension decay occurs earlier in isotonic than isometric contractions and a stretch applied at or after the peak of isometric twitches promotes a faster relaxation: this load dependence of relaxation is less pronounced in atrial specimens. The decay of activation, evaluated from the decline of the muscle shortening ability, is faster in atrium than in ventricle. These findings suggest that the sensitivity of relaxation to the loading conditions might be determined by both the activation decay rate and the cross bridge kinetics.

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When caffeine plus calcium is added to the perfusing medium, isometric relaxation of rat myocardium is no longer affected by length changes occurring during the twitch. The dependence of isometric relaxation on the initial muscle length is still present and more pronounced after caffeine addition.

The possible mediation of muscarinic and/ or nicotinic-cholinergic receptors in the response of ACTH to insulin-induced hypoglycaemia was evaluated in 18 normal men. Subjects were tested with the insulin (0.15 U/kg) tolerance test (ITT) in basal conditions and in the presence of the M1-and M2-muscarinic antagonist atropine (600 \g=m\g iv just before insulin injection (time 0) plus 600 \ g=m\ g 20 min later in 6 subjects) or the M1-muscarinic receptor blocker pirenzepine (40 mg iv 10 min before ITT or 20 mg at time 0 plus 30 mg at time 20 in 6 subjects). The remaining 6 men were treated with the nicotinic receptor antagonist trimethaphan (0.3 mg/min \m=x\30 min before ITT). ACTH rose 4.7 times in response to hypoglycaemia. The ACTH response to hypoglycaemia did not change after pirenzepine administration, whereas it was significantly increased by atropine and decreased by trimethaphan treatment. These data indicate that nicotinic and muscarinic (M2 but not M1) receptors participate in a different manner in the regulation of the hypoglycaemia-induced ACTH release.Acetylcholine is known to play a role as neurotransmitter in the regulation of ACTH secretion (Delitala 1984). However, the data available in the literature are very scant and, particularly, the precise role of muscarinic and nicotinic receptors has not yet been clarified. A paper of Evans & coworkers (1986) demon¬ strated that muscarinic-cholinergic blockade with atropine facilitates the ACTH response to insulininduced hypoglycaemia. However, atropine can¬ not distinguish between Mi-and M2-receptors (Weiner 1985). In the present study we tried to get a better insight into this problem. The recent availability of the selective M muscarinic antago¬ nist pirenzepine (Hammer & Giachetti 1982; Wat¬ son et al. 1984) gave us the opportunity to estab¬ lish whether the effect of atropine was exerted through Mi-or M2-muscarinic receptors. In addi¬ tion, we tested the effect of the blockade of nicotinic-cholinergic receptors with the specific antagonist trimethaphan (Taylor 1985) on the ACTH response to insulin-induced hypoglycae¬ mia. For this purpose, an insulin tolerance test (ITT) was performed in normal men with and without previous treatment with atropine, piren¬ zepine or trimethaphan. Subjects and MethodsEighteen healthy male subjects between the ages of 23 and 36 years participated in this study after giving informed consent. All of them were within 15% of their ideal body weight. None of the subjects was taking any drug. Each subject was tested at least twice on different days. Tests were performed in random order with a