KentAfter blockade of myocardial, but not coronary vascular 13-adrenoceptors by practolol, cardiac sympathetic stimulation or exogenously administered noradrenaline gave rise to coronary vasoconstriction, possibly due to stimulation of coronary a-adrenoceptors.The decrease in coronary vascular resistance that normally accompanies the chronotropic and inotropic effects of sympathetic nerve stimulation or administration of catecholamines, thereby satisfying the increased myocardial oxygen requirement, converts to an increase in the presence of propranolol (Feigl, 1967;Gaal, Kattus, Kolin & Ross, 1966). Since this increase in coronary resistance might occur in patients undergoing propranolol therapy (Parratt, 1967), the suggestion by Parratt & Wadsworth (1970) left ventricular pressure (dp/dt max.) occurred in five dogs, the mean reduction being 16+8%. Coronary vascular resistance was increased by 9-3 +2-1 % (P<005) and coronary flow reduced by 20+7% (P

The effects of tolamolol, propranolol and practolol on both isoprenaline-and exerciseinduced tachycardia have been studied in conscious dogs. Tolamolol was approximately equipotent to propranolol and 50 times more potent than practolol in antagonizing exerciseinduced tachycardias, but was approximately 12 times less potent than propranolol and 8 times more potent than practolol in blocking isoprenaline-induced tachycardia. It is suggested that antagonism of the tachycardia induced by exercise affords a more meaningful assessment of the possible therapeutic potential of /8-adrenoceptor blocking drugs than does that induced by isoprenaline.

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1. The effects of bretylium on the excitation of postganglionic adrenergic C fibres by acetylcholine and the release of noradrenaline by acetylcholine and electrical stimulation of the splenic nerves have been studied using the in situ and cross perfused cat spleen.2. Close arterial injections of acetylcholine (10-200 gg) evoked a brisk asynchronous discharge in fine filaments of the splenic nerve which reduced the height of the orthodromic C fibre compound action potential. 3. Hexamethonium abolished both the excitation of C fibres and release of noradrenaline by acetylcholine, whereas the liberation of noradrenaline by electrical stimulation of the splenic nerves remained unchanged. 4. Bretylium (0.5 and 1.0 mg) given close arterially blocked the output of noradrenaline and contractions of the spleen that occurred in response to nerve stimulation (30 c/s) but had much less effect on the responses to acetylcholine. 5. Bretylium (2-4 mg) given close arterially blocked the output of noradrenaline and contractions of the spleen caused by both nerve stimulation (30 c/s) and acetylcholine. 6. The close arterial injection of (+)-amphetamine sulphate (100 jug) after bretylium (2-4 mg) partially restored the output of noradrenaline and contractions of the spleen to both nerve stimulation and acetylcholine. 7. The difference in the sensitivity to blockade by bretylium of the effects of nerve stimulation and the sympathomimetic effects of acetylcholine did not exist if the more "physiological" frequency of stimulation of 10 c/s was employed.8. The close arterial injection of acetylcholine (100 jug) caused a mean average fibre discharge frequency of 5.4 spikes/sec. 9. Bretylium in amounts sufficient to completely block the sympathomimetic effects of acetylcholine did not alter the excitation of C fibres by acetylcholine. 10. The significance of these results is discussed both in relation to the mode of action of bretylium and to the use of these differential effects of bretylium as evidence for the " cholinergic link " hypothesis. Farber (1936) first described the sympathomimetic effect of acetylcholine on the spleen which was reinvestigated by Daly & Scott Brandon &Rand (1961).

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