Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, C95
Dehydroepiandrosterone treatment reduces expression of inflammatory mediators in aorta from ovariectomized rats
J. G. Camporez1, E. H. Akamine2, A. P. Davel1, L. V. Rossoni1, C. O. Carvalho1
1. Department of Physiology and Biophysics, University of Sao Paulo, S?o Paulo, S?o Paulo, Brazil. 2. Department of Pharmacology, University of Sao Paulo, S?o Paulo, S?o Paulo, Brazil.
Proinflammatory cytokine such as TNF-α, IL-1β and IL-6 are involved in the pathogenesis of some vascular disorders. Cardiovascular disease is much less frequent in premenopausal women than in age-matched men or postmenopausal women. Moreover, the marked age-related decline in serum dehydroepiandrosterone (DHEA) level has been associated to cardiovascular disease. The aim of this study was to evaluate the effects of DHEA on vascular function and expression of inflammatory mediators in aorta from ovariectomized rats. At 8 weeks of age, female Wistar rats were anesthetized with a ketamine-xylazine mixture (90 and 5 mg/kg i.p.) and were ovariectomized (OVX) or sham (SHAM) operated. Eight weeks after surgery, OVX and SHAM were treated with vehicle or DHEA (10 mg/kg/week, s.c.) for 3 weeks. At the end of treatment, aortic rings were isolated to evaluate the vasoconstrictor response to phenylephrine (PHE, 100 pM - 100 μM) and the relaxation responses to acetylcholine (ACh, 10 pM - 10 μM) and sodium nitroprussiate (SNP, 10 pM - 10 μM). The vascular reactivity was studied in rings incubated with sodium salicylate (NaSal; 5 mM). TNF-α, IL-1β and IL-6 protein expression was quantified by Western blot. Maximal response (Emax) to PHE was increased in rings from OVX compared to SHAM (SHAM: 0.84 vs. OVX: 1.27 g of tension/mg of tissue, p < 0.01). In addition, Emax to ACh was reduced in rings from OVX compared to SHAM (SHAM: 91 vs. OVX: 74% of relaxation, p < 0.01), whereas, there was no change on SNP-induced relaxation. Treatment of DHEA in OVX rats (OVX+DHEA) corrected the increased Emax to PHE (OVX+DHEA: 0.90 g of tension/mg of tissue) and the impairment on ACh-induced relaxation (OVX+DHEA: 90% of relaxation). Moreover, 1 hour of NaSal incubation induced a significant reduction of Emax values to PHE and an increase on ACh-induced relaxation in aorta from OVX. In addition, TNF-α and IL-1β protein expression was increased in aorta from OVX and normalized by treatment of DHEA (SHAM: 1.0 vs. OVX: 1.7 vs. OVX+DHEA: 1.1 fold increased, p < 0.05 to TNF-α; and SHAM: 1.0 vs. OVX: 2.0 vs. OVX+DHEA: 1.3 fold increased, p < 0.05 to IL-1β), while, there was no change in IL-6 protein expression. This study demonstrates the role of proinflammatory cytokine (TNF-α and IL-1β) on vascular dysfunction in OVX rats, as well as indicates the role of DHEA as anti-inflammatory, modulating the PHE and ACh response in aorta.
Where applicable, experiments conform with Society ethical requirements