Orchidectomy enhances the effects of phenylephrine in rat isolated portal vein

Abstract

1. Orchidectomy results in long-term testosterone deprivation similar to that observed in male clinical pathologies, such as hypogonadism and age-related reductions in plasma testosterone concentrations. Although the vascular effects of these sorts of hormone deprivations are known in arteries, they have not been studied to the same extent in veins. 2. The aim of the present study was to determine the effect of orchidectomy, with or without subsequent testosterone replacement (started 23 days after orchidectomy; 10 mg/kg, i.m., testosterone propionate once every 5 days for 3 weeks), on responses of rat isolated portal veins and vena cavae to exogenous phenylephrine (PE). Isolated vessels were mounted in an organ bath and concentration-response curves constructed to PE (10(-10)-10(-4) mol/L), endothelin (ET; 10(-10)-10(-5) mol/L) and KCl (10(-2)-1.2 x 10(-1) mol/L; as a control). 3. Orchidectomy had no effect on contractile responses of either the portal vein or vena cava to KCl. However, orchidectomy enhanced the maximum response (R(max)) of the portal vein, but not the vena cava, to PE. Testosterone replacement had no effect on these responses. The effects of orchidectomy on the R(max) to PE in portal veins were not altered by the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (10(-4) mol/L) alone or combined with 10(-5) mol/L indomethacin (a non-selective cyclo-oxygenase inhibitor), but they were abolished following treatment of isolated vessels with the ET(A) and ET(B) receptor antagonists BQ-123 and BQ-788 (both at 10(-6) mol/L). Orchidectomy did not alter portal vein responses to the application of exogenous ET. 4. The results of the present study indicate that orchidectomy-induced decreases in plasma testosterone can increase the venoconstrictor effects of PE on the portal vein and that this effect involves activation of both ET(A) and ET(B) receptors by locally produced ET.

Orchidectomy enhances the expression of endothelin-1 and ET_B receptors in rat portal vein

“…Real-time PCR was chosen in in this study because the portal vein of rats is small and the use of direct methods of quantification of peptides is difficult. Nevertheless, since the presented data are congruent with those previously obtained in functional experiments (12), this limitation does not invalidate the hypothesis that orchidectomy increases the synthesis of ET-1 and ET B receptors in rat portal vein.…”

“…On the other hand, neither orchidectomy nor testosterone replacement treatment in orchidectomized animals modified the local expression of ET A receptors. However, this orchidectomy-induced increment of the ET B genic expression was not followed by modification of the rat portal vein responses to exogenous ET-1 (12). Perhaps this indicates a simultaneous action on ET B receptors overexpressed in both endothelium, where they promote the release of vasodilating substances (19), and also in vascular smooth muscle.…”

“…The reported increment of the phenylephrine effects induced by orchidectomy on the rat portal vein was not observed in the presence of ET A and ET B receptor inhibitors (12). In the analyzed rat portal veins, the genic expression of ET B receptors was not only increased by orchidectomy but also restored by testosterone replacement treatment.…”

“…The orchidectomy as well as the testosterone replacement therapy was performed in accordance with the protocol described (12). Briefly, under anesthesia with 2,2,2-tribromoethanol (Acros Organics, Geel, Antwerp, Belgium; 250 mg/kg, i.p.…”

“…This orchidectomy-induced increase of response was not observed in the presence of either BQ-123 or BQ-788, selective antagonists of ET A and ET B receptors respectively (12). Based on these data, we can infer that orchidectomy increases the expression of endothelin-1 and/or ET A and ET B receptors in the rat portal vein, thereby resulting in elevation of portal vein responses to phenylephrine.…”