Comparison of the Effects of Castration and Streptozotocin-Induced Diabetes mellitus on Contractile Responses of the Rat Vas deferens

Abstract

Contractile responses of androgen-sensitive smooth muscles such as the vas deferens and seminal vesicles are highly dependent upon the endocrine status of the animal. Although diabetes mellitus produces disturbances in reproductive function, including decreased serum androgen levels, the effects of diabetes on the contractile function of androgen-dependent urogenital smooth muscles have not been conclusively established. The present study compared the effects of streptozotocin-induced diabetes with those of castration on the contractile responses of rat vasa deferentia. Diabetes and castration produced significant decreases in serum testosterone levels, accompanied by significant decreases in vas deferens weights. Contractile responses of vasa deferentia from diabetic rats to carbachol, ATP, and phenylephrine were significantly increased, and responses to nerve stimulation were decreased. Similar results were obtained with vasa deferentia from castrated rats. Castration produced significant increases in contractile responses of vasa deferentia to carbachol and phenylephrine and decreased responses to nerve stimulation. The data suggest that both castration and diabetes produce a denervation-like supersensitivity which is specific for receptor-mediated processes.

Postnatal androgen deprivation dissociates the development of smooth muscle innervation from functional neurotransmission in mouse vas deferens

“…Therefore despite many weeks of androgen deprivation, full function was regained and there was no postnatal critical period for development or maturation of neuroeffector transmission. Similar studies have not been reported elsewhere, although various studies have shown that replacement of testosterone following adult castration is effective in restoring tissue weight, noradrenaline and dopamine β-hydroxylase content and mechanical responses to exogenously applied contractile agents and nerve stimulation (Wakade et al 1975;MacDonald & McGrath, 1980;Bustamante et al 1989;Longhurst et al 1989;Pupo, 1989;Longhurst, 1990;Campos et al 2003). The present study has not examined the cellular mechanism of action of testosterone to 'rescue' normal neurotransmission in hpg mice.…”

“…Despite the apparent absence of noradrenergic transmission in vasa deferentia from castrated adult rats, these tissues are contracted by exogenously applied α 1 ‐adrenoceptor agonists. These agents have usually produced tonic contractions (Calixto & Rae, 1981; Longhurst et al 1989; Pupo, 1989; Longhurst, 1990; Campos et al 2003), whereas MacDonald & McGrath (1980) reported phasic responses that resemble those in longitudinal muscle of hpg vasa deferentia. However vasa deferentia from castrated rats typically display ongoing spontaneous contractions like those observed in hpg and hpg T vasa deferentia (MacDonald & McGrath, 1980; Pupo, 1989; Campos et al 2003).…”

Effect of diabetes and elevated glucose on nitric oxide‐mediated neurotransmission in rat anococcygeus muscle

“…Dysfunction of the autonomic nervous system is an important complication of diabetes mellitus contributing to alterations in cardiovascular, gastrointestinal and genitourinary function (Hosking et al, 1978;Clarke et al, 1979). Morphological, histological and functional alterations in autonomic neurotransmission have been reported for noradrenergic, cholinergic, 5-hydroxytryptaminergic, peptidergic and purinergic nerves (Lincoln et al, 1984;MacLeod & McNeill, 1985;Longhurst & Belis, 1986;Nowak et al, 1986;Belai et al, 1985;Mathison & Davison, 1988), using experimental animal models of diabetes mellitus, in particular the streptozotocin (STZ) diabetic rat. However, few studies have examined the effects of the diabetic state on nonadrenergic noncholinergic (NANC) inhibitory neurotransmission mediated by nitric oxide (NO), or nitrergic neurotransmission.…”

Castration Induces Down-Regulation of A-Type K+ Channel in Rat Vas Deferens Smooth Muscle

“…Previous studies have suggested that (i) Kv7 channel β subunits (KCNE1-3) and the Na + channel β 2 subunit (Navβ 2 ) modulate Kv4 channel properties in cardiac muscles and neurons [21,22], and (ii) significant decreases in serum testosterone levels might cause a switch in A-type K + channel genes from Kv4.2 to Kv1.4 in cardiac muscles [3,15]. We compared the expression levels of KCNE1-3, Navβ 2 , and Kv1.4 in the four groups and found that their expression relative to ACTB was markedly less than 0.01 in the VDSMs of the four groups, with no significant changes being detected.…”

“…The testosterone-mediated development of the Wolffian duct is regulated by a number of growth factors, including epidermal growth factor (EGF), insulin-like growth factor (IGF), and fibroblast growth factor (FGF) [2]. Castration significantly decreases serum testosterone levels, and this is accompanied by significant reductions in the weight of the vas deferens (VD) [3]. Previous studies reported that spontaneous contractions appeared in the VD of castrated animals, and testosterone replacement suppressed these phenomenon [4,5,6].…”