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dc.contributor.authorLabazi, Hicham
dc.date.accessioned2022-02-28T22:15:02Z
dc.date.available2022-02-28T22:15:02Z
dc.date.issued2012-12
dc.identifier.urien
dc.identifier.urihttp://hdl.handle.net/10675.2/624203
dc.description.abstractCardiovascular diseases, which are the leading cause of illness and death in the United States, frequently share similar risk factors (hypertension, smoking, aging, etc ... ) as erectile dysfunction (ED). Hypertension is an important risk factor for both heart failure and ED; hypertension and ED are closely intertwined diseases, which have "ascular and endothelial dysfunction as a common cause. Recently it has been shown that ED is an independent predictor of cardiovascular diseases (CVD). Thus, studying mechanisms of erectile function and ED will be of great importance for developing treatments for ED, as well as reducing the burden of CVD. Tn this dissertation, the mechanisms of angiotensin II (Angll)-induced ED was investigated. ln addition, we also investigated the effect of metformin on erectile function in an Angii-hypertensive model of ED. We hypothesized that Angll infusion for 4 weeks results in ED and treatment with metformin improves erectile function in the Angll-infused rats. We observed that AngTI infusion resulted in ED, which was accompanied by an increased contraction and decreased relaxation response of the corpus cavemosum and pudendal arteries. Furthermore, it was observed that ERK I /2 activation contributes to ED in the Angllhypertensive model of ED. Treatment with metformin restored erectile function in AngTIhypertensive rats, with a reversal of the increased contractility and decreased relaxation seen in both the corpus cavernosum and pudendal arteries of the hypertensive rats. Our data suggest that metformin may have potential therapeutic effects in ED, independent of its anti-diabetic effects. Additionally we investigated the contribution of nitroxyl anion (HNO), a NO congener, to erectile function. We observed that the endothelium mediated relaxation in pudendal arteries was partially mediated through I INO, and that this relaxation was soluble guanylyl cyclase-dependent (sOC), resulting in activation of voltage-dependent potassium channels (Kv) and large conductance calcium-activated potassium channel (BKca). The identification of this novel pathway will enhance our understanding of erectile function and possibly allow for development of therapeutic agents for the treatment of ED.en_US
dc.language.isoen_USen_US
dc.publisherAugusta Universityen_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.titleNitroxyl anion as a novel relaxant molecule in the rat pudendal artery and metformin as treatment for angiotensis II-induced erectile dysfunctionen_US
dc.typeDissertationen_US
dc.contributor.departmentMedical College of Georgiaen_US
dc.description.advisorWebb, Clinton
dc.description.committeeErin
dc.description.committeeBollag
dc.description.committeeMong
dc.description.committeeDong
dc.description.committeeCaldwell
dc.description.committeeTostes
dc.description.degreeDoctor of Philosophyen_US
dc.embargoen
refterms.dateFOA2022-02-28T22:15:03Z


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