Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy

Abstract

1 The effects of some sympathomimetic amines and of carbachol and potassium chloride upon the contractility of epididymal halves of the rat vas deferens have been examined in vitro at several times following vasectomy by medial transection of the vas deferens in vivo. The inhibitory effects of noradrenaline and the excitatory effects of potassium chloride upon prostatic halves of transected tissues were also studied. 2 Partially denervated epididymal segments, taken 2 days after surgery, were spontaneously active, and responses to KCl (80 mmol/l) and maximum responses to phenylephrine were enhanced. These effects were not observed with preparations taken at later times. Spontaneous activity and enhancement of responses to KCl were abolished by guanethidine (0.1 mumol/l). 3 Supersensitivity to noradrenaline was observed in fully denervated epididymal halves of vasa deferentia taken 7-183 days after transection. The supersensitivity consisted of a leftward shift in the log concentration-response curves for noradrenaline constructed upon operated, relative to those obtained upon unoperated preparations. Supersensitivity to phenylephrine but not to methoxamine or to carbachol was also evident. 4 The magnitude of the leftward shift in the log concentration-response curve for noradrenaline in operated epididymal segments approached that produced, in unoperated segments, by nisoxetine (0.1 mumol/l). This inhibitor of neuronal uptake did not enhance the potency of noradrenaline in operated segments. 5 Prazosin (50 nmol/l) antagonized the effect of phenylephrine upon both operated and unoperated epididymal segments. The antagonism was significantly greater upon operated segments than upon unoperated segments 4 and 28 days after surgery. 6 In prostatic segments, noradrenaline produced inhibition of field stimulation-induced twitches. Its potency was similar in both operated and unoperated preparations, and nisoxetine (0.1 mumol/l) potentiated its effects to a similar extent (approximately 70-fold) in control and operated tissues. Responses to KCl in this half of the vas deferens were essentially unaffected by vasectomy. 7 Taken together, these findings indicate that post-ganglionic denervation of the epididymal half of the rat vas deferens by medial transection (vasectomy) leads to a slowly developing and prolonged supersensitivity to noradrenaline which is primarily due to the loss of the neuronal uptake facility. Persistent adaptive changes in the effector cells are apparently minimal after this means of denervation.

Subsensitivity to Atp and Some Analogues in Preparations of Rat Cauda Epididymis and Vas Deferens After Vasectomy

“…Thus, the effects of this procedure upon the putative co-transmitter ATP were opposite to those observed for noradrenaline (DeGaris & Pennefather 1987a;Ventura et al 1989a). Partial re-innervation of epididymal segments after vasovasostomy did not reverse the subsensitivity to AppNHp.…”

“…The present findings indicate that subsensitivity, rather than supersensitivity, to ATP, AppNHp and P-ymATP usually develops in segments of epididymal halves of vasa deferentia and cauda epididymides after vasectomy. Thus, the effects of this procedure upon the putative co-transmitter ATP were opposite to those observed for noradrenaline (DeGaris & Pennefather 1987a;Ventura et al 1989a). Partial re-innervation of epididymal segments after vasovasostomy did not reverse the subsensitivity to AppNHp.…”

“…Associated with this is development of a prejunctional supersensitivity to noradrenaline in the epididymal segment of the operated vas deferens (DeGaris & Pennefather 1987a). This is also seen in preparations of cauda epididymis from the operated side (Ventura et al 1989a).…”

Noradrenergic Reinnervation of the Rat Vas Deferens After Vasovasostomy Following Vasectomy

“…Stimulation of epididymal segments was discontinued. Half an hour later cumulative log concentration-response curves for noradrenaline were constructed on both segments, first in the absence and then in the presence of nisoxetine (0.1 pmol/l) as described in detail previously (Leedham et al 1985;DeGaris & Pennefather 1987). Mean neg log EC50 values for noradrenaline, and mean maximal responses to noradrenaline were determined from mean log concentration curves in each group of tissues.…”

“…Rapid and long-lasting loss of catecholamine fluorescence, noradrenaline content and of response to field stimulation in the epididymal segment of the transected vas deferens occurs in vitro. A moderate but selective supersensitivity to noradrenaline, associated with the loss of noradrenaline uptake follows the surgical procedure (DeGaris & Pennefather 1987).…”