Angiotensin I-converting enzyme (ACE) inhibitors exert their pleiotropic anti-inflammatory effects on patients with arterial hypertension or congestive heart failure. However, the effects that ACE inhibitors have on pro-inflammatory and anti-inflammatory cytokines levels in male and female SHR still remain unclear. So, this study was designed to investigate the interaction between the renin-angiotensin system (RAS) and sex hormones and the effect that this interaction has on inflammatory biomarker (interleukin (IL)-10, IL-6, TNF-α) levels in spontaneously hypertensive rats (SHR) rats. The procedures were carried out in compliance with the guidelines for the ethical use of animals in scientific research and were approved by the Ethical Committee of the Federal University of Espírito Santo. All of the surgical procedures were carried out under ketamine (70 mg/kg i.p.) and xylazine (10 mg/kg i.p.) anesthesia. Rats were divided into 4 experimental groups (n: 7) that consisted of female and male SHR: sham + vehicle (SV), sham + enalapril (SE; 10 mg/kg body weight), castrated + vehicle (CV), and castrated + enalapril (CE). The treatments began 21 days after castration and lasted for 30 days. The systolic blood pressure, plasma cytokine levels and angiotensin I-converting enzyme (ACE) activity of the rats were measured by tail-cuff, ELISA and fluorimetry, respectively. Values are means ± S.E.M., compared by ANOVA. The IL-10 (p<0.05, SVF: 16.4±1.1 pg/ml vs SVM 12.8±1.2 pg/ml), TNF-a (p<0.05, SVF: 16.6 ± 1.2 pg/ml vs SVM: 12.8±1 pg/ml) and IL-6 (p<0.05, SVF: 10.3 ± 0.2 pg/ml vs SVM: 7.2 ± 0.2 pg/ml) levels were higher in female rats than male rats. The ovariectomy procedure reduced the levels of all of the cytokines. The orchiectomy reduced the IL-6 concentrations and increased the IL-10 concentrations in the male rats. Castration changed the previous pattern of response, eliminated the differences in inflammatory cytokine levels between the males and females and reduced the IL-10 levels in females. Enalapril equilibrated the cytokine levels of the male and female groups and increased the IL-10 concentration in all of the treated groups. However, the pro-inflammatory cytokine concentrations did not change in the castrated groups. In conclusions, sexual dimorphism was observed in the plasma cytokine levels of the SHR. ACE inhibition eliminated the sexual dimorphism observed in hypertensive animals, a finding that demonstrates the influence of RAS on the levels of these cytokines.
Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, C35
Oral Communications: Gender dimorphisms in the plasma IL-10, TNF-a and IL-6 levels of spontaneously hypertensive rats: the role of the renin-angiotensin system
P. L. Dalpiaz1, A. Z. Lamas1, I. F. Caliman1, A. S. Medeiros3, M. F. Alves2, A. K. Carmona2, N. S. Bissoli1
1. Department of Physiological Sciences, UFES, Vit¾ria, Brazil. 2. Department of Biophysics, Escola Paulista de Medicina, , Federal University of SÒo Paulo, SÒo Paulo, Brazil. 3. Biological and Health Sciences, Federal Institute of Espirito Santo, Vila Velha, Brazil.
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Where applicable, experiments conform with Society ethical requirements.