Orchidectomy enhances the effects of phenylephrine in rat isolated portal vein

P>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 NG-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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The possible involvement of hyperpolarizing mechanisms in histamine-induced relaxation of the rat portal vein

The present study evaluated the effects of histamine 10 -2 M on longitudinal preparations of rat portal vein. It was observed that histamine 10 -2 M induced relaxation of rat portal vein preparations pre-contracted with phenylephrine 10 -4 M. On the other hand, no pharmacological effects were observed in preparations not pre-contracted. The observed histamine-induced relaxing effect was absent in preparations pre-contracted with KCl (120 mM) or in the presence of depolarizing nutritive solution. However, the histamine-induced relaxation was still present in the endothelium-removed preparations. The histamine-induced relaxation also was not prevented by astemizole (10 -6 M, 10 -5 M and 10 -4 M), cimetidine (10 -5 M, 10 -4 M and 10 -3 M) or thioperamide (10 -6 M, 10 -5 M and 10 -4 M), selective antagonists H 1, H 2 and H 3, respectively. The presence of L-NAME 10 -4 M or L-NAME 10 -4 M plus indomethacin 10 -5 M also did not prevent the histamine-induced relaxation observed in rat portal vein. Thus, the histamine-induced relaxation observed in rat portal vein appears to involve a non-endothelial hyperpolarizing mechanism independent of H 1, H 2 and H 3 receptors

The enigmatic role of cholinergic reflex in the pathogenesis of Chagas disease

This study evaluated the inflammatory process in the colons of mice infected with Trypanosoma cruzi QM2 strain, through the analysis of muscle reactivity and the measurement of butyrylcholinesterase (BuChE) in plasma. Swiss mice were infected with T. cruzi QM2 strain and after 15 (G15), 30 (G30), 60 (G60), 90 (G90), and 210 (G210) days, each group had blood collected for the measurement of butyrylcholinesterase plasma concentrations ([BuChE]), a measure which functioned as an indicator of plasmatic Ach levels. All groups, except G15, had a segment of proximal colon removed to assess muscle reactivity to acetylcholine (Ach) and noradrenaline (NA) stimulation. After reactivity tests, the tissues were then fixed and stained with hematoxylin and eosin (HE) for histological evaluation of inflammatory response. The QM2 strain did induce inflammatory process in mice colon, and demonstrated differences in muscular contraction between the G60 and G210 groups, with p < 0.05. Plasma [BuChE] increased during the acute phase of infection (p < 0.05) with subsequent heterogeneous decline in the late chronic phase. These results show that the QM2 strain has tropism to the colon of mice and causes damage characteristic of megacolon; also, Ach has an enigmatic importance in the anti-inflammatory reflex over the course of T. cruzi infection.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP