Several neurotrophins as neurotrophin NT NT

Several neurotrophins as neurotrophin 3 (NT‐3), NT‐4, and nerve growth factor (NGF) are known to have a positive effect on the nerve dysfunction in diabetic cavernous tissue [5]. The latter is even suggested to mediate the action of CGRP [6]. Calcitonin gene‐related peptide (CGRP) is an important neuropeptide involved in penile erection [7]. It is present in the central and peripheral nervous system, mainly in close approximation with blood vessels [8] while in the periphery, it is located in small, unmyelinated sensory C fibers and myelinated type A fibers [9]. CGRP is a potent arterial and venous vasodilator that acts directly on the smooth muscles to stimulate adenylate cyclase enzyme. The resulting rise in cyclic adenosine monophosphate (cAMP) activates protein kinase A, which cause opening of potassium channels, leading to muscular relaxation [10]. On the other hand, various pathological changes affect the endothelial Exendin-3 (9-39) amide and smooth muscle of corpus cavernosum in diabetic patients. They lead to endothelial dysfunction, increased the contractile susceptibility of the smooth muscles with decreased response to the relaxation factors and finally fibrosis and atrophy of the corpus cavernosum [11].
Material and Methods
Discussion The rat model in particular provides the most valuable and reproducible investigations that significantly contributed to male sexual dysfunction as well as in the development of various treatment modalities [15]. Furthermore, diabetic rats start to develop dysfunctional erectile responses after 6 weeks of induction of diabetes contrarily to half of diabetic men who usually suffer from ED within 10 years of diagnosis of DM [16,17]. With regard to the changes in the FBG level in group II rats (diabetic), it ranged between 350 and 500 mg/dL with progressive significant increase along the first 4 weeks of the present study, with no further significant elevations during the remaining 4 weeks of the study. This may be explained by the progressive damage of beta cells of islets of Langerhans by STZ due to necrosis and apoptosis up to a point where no significant further damage could occur. This is consistent with the findings of other studies that proved the destructive capacity of STZ to the pancreas [18]. CGRP is one of the most potent vasodilators in the body and is postulated to play a role in penile erection. It is found in large amounts in axons innervating the penis of rats, dogs, monkeys, and humans [19,20]. In fact, neurotrophins such as NGF, brain‐derived neurotrophic factor, and NT‐3 are upregulated in the cavernous tissue of diabetic rats with ED [21]. They play an important role in the repair and regeneration of injured nerves as well as regulating the development and function of postganglionic sympathetic and sensory neurons [22]. NGF in particular has an important role in the growth and maintenance of function of sensory nerves [23]. At a cellular level, NGF upregulates CGRP via a cAMP/ras responsive element [6], and via a constitutively active mitogen‐activated protein kinase. In some experiments, the upregulation of CGRP was associated with nerves sprouting, an indication of NGF activity [24]. That is why the increased CGRP level in the current study might result from compensatory increase in the neurotrophin NGF. The results of the present study are consistent with another study by Morrison et al., who found a significant elevation of CGRP in the rats corpora cavernosa after 12 and 16 weeks of induction of type I DM, though they did not report the early steady changes in the level of CGRP as in the current study [12]. Further studies elucidated the possible protective role of CGRP. It is involved in the mediation of ischemic preconditioning in the heart, heat stress reaction, drug‐induced preconditioning, and in endothelial protection [25]. In the present work, in contrast to the expected, no further significant increase in the level of CGRP occurred in the 8th week of DM compared to the 6th week. Other investigators even found that diabetes caused a decrease rather than an increase in CGRP content [26].