Can vitamins C and E restore the androgen level and hypersensitivity of the vas deferens in hyperglycemic rats?

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Immunolocalization of aquaporins 1, 2 and 7 in rete testis, efferent ducts, epididymis and vas deferens of adult dog

The transepithelial movement of water into the male reproductive tract is an essential process for normal male fertility. Protein water channels, referred to as aquaporins (AQPs), are involved in increasing the osmotic permeability of membranes. This study has examined the expression of AQP1, AQP2, and AQP7 in epithelial cells in adult dog efferent ducts, epididymis, and vas deferens. Samples of dog male reproductive tract comprising fragments of the testis, initial segment, caput, corpus and cauda epididymidis, and vas deferens were investigated by immunohistochemistry and Western blotting procedures to show the localization and distribution of the AQPs. AQP1 was noted in rete testis, in efferent ducts, and in vessels in the intertubular space, suggesting that AQP1 participated in the absorption of the large amount of testicular fluid occurring characteristically in the efferent ducts. AQP2 expression was found in the rete testis, efferent ducts and epididymis, whereas AQP7 was expressed in the epithelium of the proximal regions of the epididymis and in the vas deferens. This is the first time that AQP2 and AQP7 have been observed in these regions of mammalian excurrent ducts, but their functional role in the dog male reproductive tract remains unknown. Investigations of AQP biology could be relevant for clinical studies of the male reproductive tract and to technologies for assisted procreation.

Vas Deferens Surface Epithelium of Agouti paca: Fine Structural Features

The surface epithelium of the vas deferens of Agouti paca, a wild and large South American rodent, was basically formed by principal and basal cells being only the principal cells related to endocytosis processes and also secretion taking base on their cytoplasmic ultrastructural features. Principal cell of vas deferens epithelium were characterized mainly by presence of vesicles with several shapes, sizes and internalized content at their apical cytoplasm occurring smaller pits and pale small vesicles seen next to the apical brush border of microvillus. Moreover, coated vesicles, smooth surface vesicles and great vesicles; multivesicular bodies, endosomes and lysosomes were seen. Presence of an apocrine secretory apparatus was also viewed, showing apical cytoplasmic expansions protruding into the vas deferens luminal compartment. The basal flattened cells, without luminal surface contact, occurred next to the basement membrane of the ductus, and did no exhibit special ultrastructural features.

Functional effects of castration on alpha(1)-adrenoceptors in rat vas deferens

The effects of castration on alpha(1)-adrenoceptors in rat vas deferens were investigated by determining the actions of selective antagonists against the contractions induced by noradrenaline. The results obtained in vas deferens from control rats suggest participation of alpha(1A)-adrenoceptors as judged by the pA(2) values for prazosin (9.6), benoxathian (9.5), 2(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxone hydrochloride) (WB 4101) (9.6), phentolamine (8.4), 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane-7,9-dionedihydrochloride (BMY 7378) (6.7) and by the insensitivity to chloroethylclonidine (100 mu M, 45 min). In vas deferens from castrated rats, WE 4101 and spiperone showed slopes lower than 1.0 in the Schild plots, suggesting participation of multiple receptors. In these organs, noradrenaline contractions were partially inhibited by chloroethylclonidine (100 mu M, 45 min), indicating participation of alpha(1B)-adrenoceptors. After chloroethylclonidine treatment, WE 4101 showed a slope not different from 1.0 in the Schild plot, resulting in a pA(2) of 9.4, which indicates an interaction with alpha(1A)-adrenoceptors. It is suggested that castration modifies the functional alpha(1)-adrenoceptors subtypes in rat vas deferens. (C) 1998 Elsevier B.V. B.V. All rights reserved.

Effects of castration and of testosterone replacement on alpha(1)-adrenoceptor subtypes in the rat vas deferens

The contractions of the rat vas deferens in response to noradrenaline are mediated through alpha(1A)-adrenoceptors. We observed participation of alpha(1B)-adrenoceptors in these contractions after castration. We now investigated the time course of this plasticity and the effects of testosterone by determining the actions of competitive antagonists on noradrenaline-induced contractions after 7, 14, 21 and 30 days of castration. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) antagonised noradrenaline-induced contractions in control and castrated rats with low pA(2) values (congruent to 6.8). In control vas deferens, WB 4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) had a slope in the Schild plot no different from 1.0, while slopes lower than 1.0 ( approximate to 0.6) were observed for vas deferens from castrated rats. Chloroethylclonidine was ineffective in the control vas while it inhibited noradrenaline-induced contractions in vasa from castrated rats and converted the complex antagonism by WB 4101 into simple competitive antagonism. Treatment of castrated rats with testosterone prevented the effects of castration. The results suggest that alpha(1B)-adrenoceptors are detectable in vas deferens from at least the 7th through the 30th day after castration and that testosterone prevents this plasticity. (C) 2003 Elsevier B.V. B.V. All rights reserved.

Functional characterisation of alpha(1)-adrenoceptors in denervated rat vas deferens

We investigated whether or not surgical denervation of the rat vas deferens changes the alpha(1)-adrenoceptor subtypes involved in the contractions to noradrenaline. Denervated vas deferens was approximate to22 times more sensitive to noradrenaline (pD(2)=7.35 +/- 0.04) than control vas (pD(2)= 6.01 +/- 0.03). This difference in noradrenaline potency was eliminated when cocaine (6 muM) was added to control vas (pD(2)=7.22 +/- 0.04). The noradrenaline-induced contractions of control and denervated vas deferens were insensitive to the alpha(1B)/alpha(1D)-adrenoceptor alkylating agent chloroethylclonidine (100 muM, 45 min). The concentration-response curves to noradrenaline in control and denervated vas deferens were competitively antagonised by prazosin (pA(2)approximate to9.6), WB-4101 (pA(2)approximate to9.5), 5-methyl urapidil (pA(2)approximate to8.4), phentolamine (pA(2)approximate to8.7), yohimbine (pA(2)approximate to6.9), BMY 7378 (pA(2)approximate to6.9) and indoramin (pA(2)approximate to8.7). After the treatment of control and denervated vas deferens with phenoxybenzamine, the partial agonist oxymetazoline antagonised competitively the concentration-response curves to noradrenaline showing pA(2) values approximate to7.4 in both groups. We conclude that noradrenaline-induced contractions in control and denervated rat vas deferens are mediated by alpha(1A)-adrenoceptors and that surgical denervation of the rat vas deferens is not able to change the alpha(1)-adrenoceptor subtypes involved in the contractions to noradrenaline.

Adrenergic response patterns in vas deferens isolated from rats under diurnal rhythms - Influence of stress

The aim of this study was to verify, by means of functional methods, whether the circadian rhythm changes adrenergic response patterns in the epididymal half of the vas deferens isolated from control rats as well as from rats submitted to acute stress. The experiments were performed at 9:00 a.m., 3:00 p.m., 9:00 p.m., and 3:00 a.m. The results showed a light-dark dependent variation of the adrenergic response pattern on organs isolated from control as well as from stressed rats. In the control group, only the phenylephrine sensitivity was changed throughout the circadian rhythm. Under the stress condition, both norepinephrine and phenylephrine response patterns were changed, mainly during darkness. The maximal contractile response to both alpha- and beta-agonist and alpha(1)-agonist was increased in the dark phase, corresponding to high plasmatic concentrations of endogenous melatonin. The vas deferens isolated from stressed rats during the light phase simultaneously incubated with exogenous melatonin showed the same pattern of response obtained in the dark phase, thus indicating a peripheric action of melatonin on this organ. Therefore, the circadian rhythms are important to the adrenergic response pattern in rat vas deferens from both control and stressed rats. In conclusion, we suggest a melatonin modulation on alpha(1)-postsynaptic adrenergic response in the rat vas deferens. (c) 2005 Elsevier B.V. All rights reserved.

The importance of androgen on noradrenergic responses of vas deferens isolated from acutely stressed rats

This study investigated the importance of androgen on responses to alpha and beta (norepinephrine) and alpha(1) (phenylephrine and methoxamine) agonists in vasa deferentia isolated from adult, immature, cryptorchid, and castrated rats submitted to swimming-induced acute stress. The participation of adrenergic nervous terminals was also investigated. Acute stress was shown to induce a significant subsensitivity to norepinephrine only in vas deferens from adult rats with normal levels of androgens. In addition, sympathetic denervation of the vas deferens prevented the appearance of subsensitivity. Subsensitivity was not seen when the experiments were carried out using phenylephrine and methoxamine. This shows that subsensitivity to norepinephrine in this acute stress situation may depend on other factors such as neuronal uptake, but not on alpha(1)-adrenoceptor response. Thus, when animals are exposed to acute stressogenic situations, this subsensitivity requires physiological levels of androgens to establish, and may also be involved in body homeostasis. (C) 1999 Academic Press.

Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade

1 the actions of the alpha(1)-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could. result in self-cancelling actions.2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) values of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively.3 When the experiments were repeated in the presence of cocaine (6 mu M) the potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0.12; slope = 1.04 +/- 0.05).4 In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06).5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA(2) values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values.

Investigation of the Effects of a1-Adrenoceptor Antagonism and L-Type Calcium Channel Blockade on Ejaculation and Vas Deferens and Seminal Vesicle Contractility In Vitro

Introduction. Premature ejaculation is one of the most common male sexual dysfunctions. Current pharmacological treatments involve reduction in penile sensitivity by local anesthetics or increase of ejaculatory threshold by selective serotonin reuptake inhibitors. a1-Adrenoceptors (a1-ARs) and L-type calcium channels are expressed in the smooth muscles of the male reproductive tract, and their activations play an important role in the physiological events involved in the seminal emission phase of ejaculation.Aim. To evaluate if the inhibition of the contractility of the vas deferens and seminal vesicle by alpha(1)-AR antagonism or the L-type calcium channel blockade can delay ejaculation.Methods. The effects of the alpha(1)-AR antagonist tamsulosin and of the L-type calcium channel blockers, nifedipine and (S)-(+)-niguldipine, on contractions induced by norepinephrine in the rat vas deferens and seminal vesicles in vitro and on the ejaculation latency of male rats in behavioral mating tests were evaluated.Main Outcome Measure. Tension development of vas deferens and seminal vesicles in response to norepinephrine in vitro and behavioral mating parameters were quantified.Results. Tension development of vas deferens and seminal vesicle to alpha(1)-AR activation was significantly inhibited by tamsulosin, nifedipine, and (S)-(+)-niguldipine. Tamsulosin displayed insurmountable antagonism of contractions induced by norepinephrine in the rat vas deferens and seminal vesicle. Ejaculation latency of male rats was not modified by tamsulosin, nifedipine, or (S)-(+)-niguldipine; however, both the number and weight of the seminal plugs recovered from female rats mated with male rats treated with tamsulosin were significantly reduced.Conclusion. Seminal emission impairment by inhibition of vas deferens or seminal vesicle contractility by L-type calcium channel blockade or alpha(1)-AR antagonism is not able to delay the ejaculation. de Almeida Kiguti LR and Pupo AS. Investigation of the effects of alpha(1)-adrenoceptor antagonism and L-type calcium channel blockade on ejaculation and vas deferens and seminal vesicle contractility in vitro. J Sex Med 2012; 9: 159-168.

Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of swimming and nandrolone decanoate treatment on vas deferens response to norepinephrine

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effect of cyproterone acetate on alpha1-adrenoceptor subtypes in rat vas deferens

Gonadal hormones regulate the expression of alpha1-adrenoceptor subtypes in several tissues. The present study was carried out to determine whether or not cyproterone acetate, an anti-androgenic agent, regulates the alpha1-adrenoceptor subtypes that mediate contractions of the rat vas deferens in response to noradrenaline. The actions of subtype selective alpha1-antagonists were investigated in vas deferens from control and cyproterone acetate-treated rats (10 mg/day, sc, for 7 days). Prazosin (pA2 ~9.5), phentolamine (pA2 ~8.3) and yohimbine (pA2 ~6.7) presented competitive antagonism consistent with activation of alpha1-adrenoceptors in vas deferens from both control and treated rats. The pA2 values estimated for WB 4101 (~9.5), benoxathian (~9.7), 5-methylurapidil (~8.5), indoramin (~8.7) and BMY 7378 (~6.8) indicate that alpha1A-adrenoceptors are involved in the contractions of the vas deferens from control and cyproterone acetate-treated rats. Treatment of the vas deferens from control rats with the alpha1B/alpha1D-adrenoceptor alkylating agent chloroethylclonidine had no effect on noradrenaline contractions, supporting the involvement of the alpha1A-subtype. However, this agent partially inhibited the contractions of vas deferens from cyproterone acetate-treated rats, suggesting involvement of multiple receptor subtypes. To further investigate this, the actions of WB 4101 and chloroethylclonidine were reevaluated in the vas deferens from rats treated with cyproterone acetate for 14 days. In these organs WB 4101 presented complex antagonism characterized by a Schild plot with a slope different from unity (0.65 ± 0.05). After treatment with chloroethylclonidine, the complex antagonism presented by WB 4101 was converted into classical competitive antagonism, consistent with participation of alpha1A-adrenoceptors as well as alpha1B-adrenoceptors. These results suggest that cyproterone acetate induces plasticity in the alpha1-adrenoceptor subtypes involved in the contractions of the vas deferens.

INVOLVEMENT OF SWIMMING-INDUCED ACUTE STRESS IN THE SENSITIVITY OF RAT VAS-DEFERENS TO NOREPINEPHRINE

1. The effects of swimming-induced stress on rat sensitivity to norepinephrine were studied.2. Through microscopic analysis of the stomach from swimming stressed rats significant ulceration was observed, confirming that the stress situation was really present.3. Sensitivity to norepinephrine either in the presence or in the absence of cocaine and propranolol in acutely swimming stressed rats was not altered significantly.4. Bilateral adrenalectomy was performed in rats 2 days before swimming and acute stress resulted in a supersensitivity to norepinephrine, indicating that adrenal glands may, at least, partially mediate the sensitivity to this drug in vasa deferentia isolated from these animals.