Simultaneous measurement of contractile effects in the circular and longitudinal smooth muscle of the rat vas deferens by drugs perfused externally or via the lumen

Abstract

1 The effects of noradrenaline and barium chloride were studied in the rat isolated vas deferens by perfusion of drugs either externally or through the lumen of the organ. Two effects were recorded simultaneously in the same preparation: (a) isometric contractions, due to the tension elicited by drugs on the external (longitudinal) smooth muscle layer and (b) pressure of internal perfusion, due to contractions of the internal (circular) smooth muscle layer. 2 It was found with the longitudinal muscle that: (a) the potency, expressed as pD2 values, and the maximum response to noradrenaline were lower if the drug was perfused internally rather than externally; (b) the differences in maximum effects were pronounced on the prostatic half but were not observed on the epididymal half; (c) the maximum response obtained by internal perfusion could be increased by simultaneously adding the same dose of drug externally; (d) when barium chloride was used instead of noradrenaline no significant differences were observed on pD2 values, but differences on maximal responses were similar to that observed for noradrenaline; (e) it was possible to block completely the effect of internal or external noradrenaline on the longitudinal muscle, by perfusing external phenoxybenzamine. In these conditions the responses of the circular muscle to the agonist were only partly blocked. 3 With the circular muscle, the differences related to internal and external perfusion were less marked than in the longitudinal muscle. However, unlike the latter, the circular layer was slightly more sensitive to drugs applied internally, in relation to pD2 values. 4 It is suggested that the difference in pD2 values may be due to the removal of noradrenaline by the neuronal uptake process, whereas the difference in maximal effect is due to the inaccessibility of part of the receptor population when drugs are added through the lumen.

Different mechanisms of action of agents acting on β‐adrenoceptors in barium‐stimulated and electrically‐stimulated rat vas deferens

“…To overcome this problem, aadrenoceptors had to be inactivated in an essentially irreversible manner by a fi-haloalkylamine. A single exposure to these agents is able to cause a persistent blockade of the contractile effects of noradrenaline, and also of dopamine, in rat vas deferens (Langeloh & Jurkiewicz, 1982;Busatto & Jurkiewicz, 1985). In the present work we used dibenamine as the alkylating agent (Furchgott & Bursztyn, 1967).…”

Some Pharmacological Properties of the Circular Smooth Muscle Layer of the Rat Vas Deferens

“…Contractions of such a preparation are measured as a shortening of the organ, due to the shortening of longitudinal muscle fibres. Contractions of the cells of the circular layer are not supposed to alter the length of the vas (Busatto & Jurkiewicz 1985).…”

“…By the use of different procedures, the circular muscle has been previously investigated by Anstey (1971), , , Anton & McGrath (1977), Anstey & Birmingham (1978, 1980, Busatto & Jurkiewicz (1985) and Souza Brito & Jurkiewicz (1984). Those authors studied mainly the innervation, contractile characteristics, and the presence of a-adrenoceptors, in the organ.…”

“…From their results, Anstey & Birmingham (1978) concluded that it is possible to record the response of the circular muscle of the guinea-pig vas deferens by techniques formerly used for other tubular organs containing smooth muscle. Busatto & Jurkiewicz (1985) described a method for perfusing the vas deferens internally and externally and simultaneously recording the contractions of the longitudinal and circular muscle layers. The main concern of the latter publication, in relation to the circular muscle, was to analyse this layer as a diffusion barrier for drugs to reach the longitudinal layer.…”

“…In addition, quantitative data as for instance pD2 values for adrenergic and cholinergic agonists, and pA2 values for the corresponding antagonists also ought to be determined. It is also unknown if the sensitivity of the circular layer, expressed through these parameters is, or is not, the same when the drugs are perfused through the lumen or externally, although some information has already been provided previously (Busatto & Jurkiewicz 1985). Finally, comparisons of drug parameters determined in the circular layer with those in the longitudinal layer are also missing.…”