Study of Heparin in Intestinal Ischemia and Reperfusion in Rats: Morphologic and Functional Evaluation

To study whether treatment with heparin (HEP) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rats were treated with HEP (100 U/kg intravenously) or saline solution (SS) before I (60 min), which was produced by occlusion of the superior mesenteric artery, and R (120 min). After I or I/R, we mounted 2-cm jejunal segment in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl, using a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Compared with the sham group, jejunal contractions were similar in the I + HEP and the I/R + HEP groups, but reduced in the I + SS and the I/R + SS groups. the jejunal enteric nerves were damaged in the I + SS and the I/R + SS, but not in the I + HEP and the I/R + HEP cohorts. These results suggested that HEP attenuated intestinal dysfunction caused by I and I/R.Universidade Federal de São Paulo, Escola Paulista Med, Dept Surg, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol, BR-04023900 São Paulo, BrazilFed Univ Great Dourados, Sch Med, Dourados, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Surg, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol, BR-04023900 São Paulo, BrazilWeb of Scienc

Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion

Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n= 8), anesthetized and divided in: Sham: submitted to operation only; group SS+ IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+ IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+ I+ AT+ R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. Results: The group SS+ IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p= 0.001) in the heart tissue. The tumor necrosis factoralpha level in plasma decrease in the treated groups when compared with SS+ IR group (p= 0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. Conclusion: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.FAPESPUniv Fed Sao Paulo, UNIFESP, Postgrad Program Translat Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Surg, Div Anesthesia Pain & Intens Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Program Pharmacol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP, BrazilUNESP, Vet Med Sch, Aracatuba, SP, BrazilUniv Fed Sao Paulo, Dept Surg, Div Cardiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Program Translat Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, UNIFESP, Postgrad Program Translat Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Surg, Div Anesthesia Pain & Intens Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Program Pharmacol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Surg, Div Cardiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Program Translat Med, Sao Paulo, SP, BrazilWeb of Scienc

Increased density of alpha-adrenoceptors in vas-deferens of spontaneously hypertensive rats (SHR), indicated by functional and receptor-binding studies

Pharmacological parameters were determined from contractile responses mediated by alpha-adrenoceptors in vas deferens from spontaneously hypertensive rats (SHR) and corresponding normotensive controls, Wistar Kyoto rats (WKY), and compared with data obtained from radioligand binding assays. Contractile responses induced in longitudinal and circular muscle layers by the alpha-adrenoceptor agonist noradrenaline (NA) and by barium chloride were recorded as described previously. in both muscle layers the maximal effects induced by NA, but not by BaCl2, were significantly greater in SHR. As a consequence, the relative responsiveness ratio (rho) for the alpha-adrenoceptor was also larger for SHR than for WKY. NA-induced contractions of both muscle layers were competitively antagonized by indoramine. the pA2 values for indoramine and pD2 values for NA were the same in SHR and WKY, indicating that alpha-adrenoceptor affinity was not changed in SHR. Additionally, binding studies with thc alpha-adrenoceptor ligand [H-3]WB4101 revealed that B(max) values were greater in the vas deferens of SHR, whereas K(d) values were not significantly different from those of WKY controls. in summary, although differences could not be detected for affinity-related parameters, a greater density of alpha-adrenoceptors was shown for SHR in receptor binding studies and this was corroborated by functional studies.ESCOLA PAULISTA MED SCH,DEPT PHARMACOL,CAIXA POSTAL 20372,BR-04034 São Paulo,BRAZILESCOLA PAULISTA MED SCH,DEPT PHARMACOL,CAIXA POSTAL 20372,BR-04034 São Paulo,BRAZILWeb of Scienc

Down-regulation of Na+/K+-ATPase alpha(2) isoform in denervated rat vas deferens

In the rat vas deferens, an organ richly innervated by peripheral sympathetic neurons, we have demonstrated recently the expression of alpha(1) and alpha(2), but not alpha(3) isoforms of the a subunit of Na+/K+-ATPase (EC 3.6.1.37), a membrane-bound enzyme of vital function for living cells (Noel et al., Biochem Pharmacol 55: 1531-1535, 1998). in the present work, we characterized, qualitatively and quantitatively, Na+/K+-ATPase a isoforms in denervated rat vasa deferentia. [H-3]Ouabain binding at concentrations defined for high-affinity isoforms (alpha(2) and/or alpha(3)) detected only one class of specific binding sites in control (C) and denervated (D) vas deferens. Although the dissociation constant was similar for both groups [K-d = 138 +/- 14 nM (C) and 125 +/- 8 nM (D)], a marked decrease in density was observed after denervation [716 +/- 81 fmol(.)mg protein(-1) (C) and 445 +/- 34 fmol(.)mg protein(-1) (D), P < 0.05]. in addition, western blotting revealed that denervated vasa deferentia produce the alpha(1) and alpha(2) isoforms but not alpha(3), just as we reported for the controls previously (Noel et al., Biochem Pharmacol 55: 1531-1535, 1998). Densitometric analysis showed a decrease of the alpha(2) isoform by about 4094 in denervated organs, in very good agreement with what was shown with the [H-3]ouabain binding technique, but no significant change in oil isoform density. Truncated alpha(1) (alpha(1)T), an isoform suggested to exist in the guinea pig vas deferens, was not detected. Altogether, our results demonstrated that Na+/K+-ATPase alpha(2) is down-regulated after sympathetic denervation of the rat vas deferens. (C) 2000 Elsevier Science Inc.Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Dept Farmacol Basica & Clin, BR-21941590 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Farmacol, Escola Paulista Med, BR-04034970 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, Escola Paulista Med, BR-04034970 São Paulo, BrazilWeb of Scienc

Autonomic dysfunction of rat jejunum submitted to cold ischemic preservation is prevented by heparin

Previous studies suggest that cold ischemic preservation (CIP) employed in small bowel transplantation promotes loss of intestinal motility due to severe lesions in autonomic enteric nerves. This autonomic dysfunction may be prevented by antioxidant agents. in this work, we investigated whether preservation with heparin prevented autonomic dysfunction of rat jejunum submitted to CIP for a long time. Jejunal segments (2 cm) of Wistar rats (12 to 16 weeks old) were preserved at 4 degrees C in Ringer's lactate solution without (-) or with (+) 100 UI/mL heparin (H). After preservation for 12 hours, H+ and H- preparations were mounted in parallel in isolated organ baths containing 10 mL Tyrode's solution at 37 degrees C for the study of neurogenic contractions evoked by electrical field stimulation (EFS; 10-30 Hz, 1-ms duration, 60 V) or by stimulation of nicotinic (NIC) or muscarinic (carbachol, CCh) cholinoceptors. the effects of NIC (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists were studied on these contractions. Contractions induced by EFS (30 Hz) were four times greater in H+ (1.02 +/- 0.12 g) versus H- (0.26 +/- 0.07 g), while contractions induced by NIC (I mmol/L) were also four times higher in H+ (1.07 +/- 0.10 g) than H(0.25 +/- 0.09 g) preparations. in addition, contractions induced by CCh (1 mmol/L) were two times higher in H+ (1.21 +/- 0.13 g) than in H- (0.65 +/- 0.10 g). EFS, NIC, and CCh contractions were inhibited by pretreatment of jejunum with HEX or ATR (1 mu mol/L/30 min), in H+ and H-. These results indicated that addition of heparin to a preservation solution attenuated the autonomic dysfunction of rat jejunum submitted to CIP for a long time.Universidade Federal de São Paulo, Escola Paulista Med, Dept Surg, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Surg, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, BR-04023900 São Paulo, BrazilWeb of Scienc

Effect of allopurinol on autonomic dysfunction in rat jejunal segments exposed to cold ischemic preservation for transplantation

Universidade Federal de São Paulo, Escola Paulista Med, Dept Surg, BR-04023900 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Surg, BR-04023900 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, São Paulo, SP, BrazilWeb of Scienc

Up-regulation of Ca2+ channels in vas deferens after chronic treatment of newborn rats with nifedipine

Radioligand binding and contraction techniques were used to verify if L-type Ca2+ charnels are modified in rat vas deferens after treatment with the blocker nifedipine (15 mug), injected at 7, 14, 21 and 28 days after birth. Vas deferens tissue was used 10, 30 and 90 days after the last injection, to verify if modifications are persistent. Binding studies with cell membranes, using [H-3]isradipine, showed an increase of the density (B-max) of Ca2+ channels by more than 60%, after 10 and 30 days, without changes of affinity (K-d). Maximal contractions (E-max) of KCl, were increased by 106% and 37%, respectively, after 10 and 30 days, without changes of apparent affinity (pD(2)). After 90 days, the values of B-max, K-d, E-max and pD(2) were not different from the controls. Differences were also not found for rats injected when adult. It is concluded that treatment of newborn, but not of adult, rats with nifedipine produced a long-lasting, though reversible, upregulation of L-type Ca2+ channels. (C) 2002 Elsevier Science B.V. All rights reserved.Universidade Federal de São Paulo, Dept Pharmacol, BR-04034970 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04034970 São Paulo, BrazilWeb of Scienc