Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/253
Title: The Effect of Aging and Lipopolysaccharide-induced Endotoxemia on Reactivity of the Vas Deferens
Authors: Hebah Sultan Thuwaini Farhan 
Supervisor: Prof. Mabayoje A. Oriowo
Keywords: Aging Lipopolysaccharide-induced Endotoxemia Vas Deferens
Issue Date: 2014
Publisher:  Kuwait university - college of graduate studies
Abstract: Smooth muscle contractility is affected by a variety of factors including aging and endotoxemia. In this study, the effect of aging and lipopolysaccharide-induced endotoxemia on reactivity of the vas deferens was examined. The epididymal portion of the vas deferens was isolated from young and aged rats and set up longitudinally in organ baths containing Krebs’ solution for isometric tension recording. The tissues were stimulated electrically and by adding noradrenaline (NA). The mechanisms responsible for any changes on reactivity of the vas deferens were investigated. The possible roles of K+ channels and calcium sensitization pathways such as RhoA/Rho-kinase and protein kinase C pathways in mediating the decreased smooth muscle reactivity in aging were evaluated in vas deferens preparations isolated from young and aged rats. The results showed that reactivity of the vas deferens to electrical field stimulation (EFS) and NA was reduced in aging and that the reduction in reactivity was most likely due to post-receptor events. EFS- and NA-induced contractions were significantly attenuated in Ca2+ free Krebs solution. Nifedipine also significantly reduced EFS- and noradrenaline-induced contractions without discriminating between young and aged rats suggesting no age-dependent loss of voltage-dependent calcium channels. Y-27632, a Rho-kinase inhibitor, reduced EFS- and NA-induced contractions in both groups but was more effective in preparations from young rats consistent with a greater role for Rho-kinase mediated calcium sensitization in young rats. GF109203X, a protein kinase C inhibitor, reduced EFS- but not NA-induced contraction of the vas deferens suggesting a prejunctional role for PKC pathway of Ca2+ sensitization in the response to EFS in aged rats. 4-AP and TEA, inhibitors of voltage-dependent K+ channel (Kv) and Ca2+-activated vi K+ channel (BKCa), respectively enhanced EFS-induced contractions in preparations from young and aged rats and were more effective in preparations from young rats suggesting a reduced role for Kv and BKCa channels in aging. LPS-induced endotoxemia reduced contractions in young and aged rats, but the reduction was greater in preparations from LPS-treated young rats. In the present study, the effect of TNF-α in aging was investigated. The results show that TNF-α reduced EFS-induced contraction of the vas deferens preparations in aged rats while having no effect on the potency of NA. It was concluded that the reduction in reactivity of the epididymal vas deferens in aging could be due to alterations in RhoA/Rho-kinase and PKC pathways of Ca2+ sensitization. In addition, LPS reduced reactivity of the epididymal vas deferens segments in both groups and the effect was greater in preparations from young rats. Further studies are required to identify the basis for the differential effect of LPS on reactivity of the vas deferens in aging.
URI: http://hdl.handle.net/123456789/253
Appears in Programs:0550 Pharmacology (M.Sc.)

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