الفهرس 
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Abstract
In the present study, in-vivo experiments were performed to study the effect of acute and subacute exposure of Pb, Cd or Al on erectile function and the possible mechanisms of their action. This included the investigation of the effect of NO modulators and the role of K+- channel transmission on their effect in rat CC, the modulatory effect of the metals under test on cholinergic and nicotinic neural transmission in rat CC. The role of α-receptors modulators and L-type Ca2+ channels in the action of them in rat CC. In-vivo experiments were performed using anaesthetized male rat model and measurement of ICP changes elicited by ES of the CN. Additionally, biochemical experiments were performed to determine the effect of HMs on serum creatinine levels, testosterone levels, TBARs and GSH levels in CC tissue and the accumulation of Pb, Cd and Al in CC homogenate. A summary of the main results and conclusion are outlined below: 1. Pb, Cd and Al show anti-erectile effect in concordance with few clinical studies, the effect is evident in acute and sub-acute treatments, they significantly reduced ICP/MAP in treated male rats. 2. The metals’ effect is independent on renal function and occurs at low doses not causing renal failure or hypertension. As far serum creatinine levels which are considered as a significant marker of renal dysfunction, they were not altered at the doses tested and under the current protocol, excluding the hypothesis that Pb, Cd or Al-induced ED may occur secondarily to renal injury.
3. In the present study the effect of Cd or Al but not Pb seems to be hormone dependent. Cd and Al significantly decreased testosterone levels in male rats following subacute administration, which may be a major mechanism underlying Cd and Al anti-erectile effect.
4. Al-treated group associated with increased level of oxidative stress manifested as a significant elevation of TBARs level. 5. In the current study, Pb, Cd or Al exhibited accumulation in rat CC. They accumulated significantly in rat CC after 7 days treatment. It can be assumed that the effect of those metals is localized in erectile tissues which seem to be sensitive to them at the tested doses.
6. Pharmacological studies showed that only Pb but neither Cd nor Al may modulate or inhibit NO/cGMP pathway in rat CC since L-arginine potentiatory effect was inhibited in presence of Pb and the anti-erectile action of Pb was blocked by NOS inhibitor and sGC inhibitor. In line, Pb may modulate K+- channel as observed in the current study, the anti-erectile action of Pb was blocked TEA, while Pb had the ability to mask diazoxide- induced potentiation in ICP in male rats.