SUMMARY The smooth muscle from the human internal anal sphincter has been investigated pharmacologically in vitro. The upper and lower parts of the sphincter responded to catecholamines in a similar manner. Noradrenaline caused contraction which could be antagonized by phenoxybenzamine. After phenoxybenzamine, noradrenaline caused relaxation which could be blocked by pronethalol. Isoprenaline caused relaxation which could be specifically prevented by pronethalol. Adrenaline was variable in its effect: low concentrations caused relaxation and high concentrations caused contraction. It is suggested that the anal smooth muscle contains a-adrenergic receptors subserving contraction and ,-receptors subserving relaxation.The lower part of the sphincter was generally insensitive to acetylcholine and nicotine whereas the upper part of the sphincter contracted with acetylcholine and regularly relaxed with nicotine. The nicotine response was antagonized by hexamethonium, procaine, and pronethalol. It is suggested that nicotine stimulated some part of the nervous mechanism in the upper part of the sphincter and that a catecholamine was the mediator of the inhibitory response.The internal sphincter of the human anus forms the inner muscle layer of the whole anal canal and is a thickened continuation of the smooth muscle of the circular layer of the rectum. The activity of the sphincter is presumably under the influence of the autonomic nervous system, but very little is known about this. This paper describes the behaviour of muscle strips obtained from the upper and lower parts of the sphincter in response to noradrenaline, adrenaline, isoprenaline, acetylcholine, and nicotine. METHODStrips 20 to 30 mm long, 1 to 2 mm wide, and about 2 mm thick were taken from either the proximal or the distal part of the human internal anal sphincter, usually from specimens obtained at abdomino-perineal excision.Each strip consisted only of the circular muscle of the sphincter with any nervous tissue that it might contain. The strips were immediately placed in a modified Krebs' solution equilibrated with 95% 02 and 5% CO,, at a temperature of 37°C. A description of the saline solution used and details of the method have been reported previously (Fishlock and Parks, 1966), the only difference being that the recording was made by means of an isotonic lever with an ink fountain attachment. By trial and error it was found that the preparation required a tension of 2.5 ±I 1.5 g to maintain a steady base-line.
Summary . The action of angiotensin on the circular and longitudinal muscle of the human colon has been studied in vitro. The ED50 value (g/ml) of circular muscle was 8.7 × 10−8 and of longitudinal muscle 3.1 × 10−8, while the corresponding figures for acetylcholine were 1.6 × 10−6 and 1.1 × 10−6, respectively. Angiotensin caused a sustained contraction associated with prolonged tachyphylaxis. . As the action of angiotensin was not antagonized by atropine, hexamethonium or procaine, angiotensin appeared to act directly on the smooth muscle of the human colon. . Lidoflazine is not a specific antagonist of angiotensin.
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