Autoradiographic Localization of Nitric
Oxide Synthase Binding Sites in Normal
and Diabetic Rat Corpus Cavernosum

Sullivan, M.; Bell, C.R.W.; Dashwood, M; Miller, Marek; Thompson, CS; Mikhailidis, DP; Morgan, RJ

doi:10.1159/000474225

Cited by 31 publications

(16 citation statements)

References 21 publications

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“…Reduced penis total (endothelial and neuronal) NOS activity and neuronal NOS levels have been reported after 4±8 months in BB/WOR and BBZ/WPR rat models of Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus [6]. In streptozotocin-diabetic rats of 2±3 months duration, increased penile endothelial and total NOS, however, was found using autoradiographic and biochemical and assays [34,35]. It is possible that changes in NOS activity are biphasic in diabetic rats, an initial increase being followed by a decline.…”

Section: Discussionmentioning

confidence: 99%

Effects of diabetes and treatment with the antioxidant α-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats

1999

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Males with diabetes mellitus have an increased prevalence of erectile dysfunction. Some of the organic causes have been studied in corpus cavernosum strips isolated from men undergoing penile prosthesis implantation. Defects in endothelium-dependent and nerve-mediated vascular smooth muscle relaxation have been found [1]. Similar deficits were noted for alloxan-diabetic rabbits [2] and recently diminished neurogenic erections were reported in streptozotocin-diabetic rats [3]. The nitric oxide (NO) systems of corpus cavernosum endothelium and nerve supply are crucial for smooth muscle relaxation and erectile Diabetologia (1999) Summary Diabetes mellitus is associated with impotence in animal models and patients. Raised reactive oxygen species contribute to diabetic neurovascular deficits, which are amenable to antioxidant treatment. Our aim was to examine the effects of streptozotocin-induced diabetes in rats and long-term treatment with the antioxidant, a-lipoic acid, on responses of an in vitro corpus cavernosum preparation. Diabetes duration was 8 weeks and preventive and reversal (4 weeks untreated diabetes, 4 weeks of treatment) studies were done. Four and 8 weeks of diabetes caused an about 41 % reduction in endothelium-dependent nitric oxide mediated relaxation to acetylcholine in phenylephrine-precontracted cavernosum. This deficit was prevented (93.9 ± 7.1 %) by treatment with a-lipoic acid; reversal studies showed 64.9 ± 19.5 % correction. Neither diabetes nor treatment with a-lipoic acid altered endothelium-independent relaxation to the nitric oxide donor, sodium nitroprusside. Stimulation of corpus cavernosum autonomic innervation caused noradrenergic-mediated contractions that were unaffected by diabetes or a-lipoic acid. Non-adrenergic, non-cholinergic nerve responses, largely dependent on nitric oxide, were seen after phenylephrine precontraction in the presence of atropine and guanethidine. Non-adrenergic, non-cholinergic stimulation caused frequency dependent relaxation to a maximum of about 40 %. Diabetes reduced this to about 25 %, however with preventive a-lipoic acid treatment, non-adrenergic, noncholinergic relaxation was in the nondiabetic range. In the reversal a-lipoic acid treated diabetic group, its deficit was corrected by 52.1 ± 14.6 %. Thus, diabetes reduces endothelium and non-adrenergic, noncholinergic nerve nitric oxide-mediated relaxation of corpus cavernosum smooth muscle, which is likely to be the organic base for impotence. Prevention and partial correction by a-lipoic acid emphasises the importance of reactive oxygen species and suggests a potential therapeutic approach. [Diabetologia (1999) 42: 343±350]

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Section: Discussionmentioning

confidence: 99%

Effects of diabetes and treatment with the antioxidant α-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats

1999

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“…In more recent studies, by using reverse transcriptase-polymerase chain reaction and immuno-histochemistry, a clear demonstration of the presence of eNOS within cavernosal smooth muscle of the rat has been made. 35 Using autoradigraphic techniques Sullivan et al 36 were able to demonstrate evidence of speci®c binding sites for NOS located within the endothelium lining the cavernosal lacunar spaces, which suggests, but does not con®rm the presence of endothelial NOS.…”

Section: Discussionmentioning

confidence: 99%

Endothelial and neuronal-derived nitric oxide mediated relaxation of corpus cavernosal smooth muscle in a rat, in vitro, model of erectile function

et al. 2000

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We set out to establish a simple, reproducible, rat in vitro model of erectile function and to use this to demonstrate the functional importance of both neuronal-and endothelial-derived nitric oxide within this animal.Two corpora cavernosal smooth muscle strips were harvested from sexually mature male Wistar rats and mounted in an organ bath for measurement of isometric tension. Following contraction with noradrenaline the strips were relaxed by the addition of either acetylcholine or sodium nitroprusside. Electrical ®eld stimulation was performed in the presence of atropine and guanethidine. Relaxation responses were repeated in the presence of methylene blue, L-arginine, L-NNA and haemoglobin AE L-arginine.Methylene blue abolishes the relaxation to acetylcholine and EFS; L-NNA and haemoglobin cause a signi®cant impairment in the relaxation response. L-arginine reverses the effect of haemoglobin.In conclusion, the inhibitory, relaxant stimulus of rat corpora cavernosa is due to both neuronal nitric oxide and endothelial-derived nitric oxide released in response to cholinergic stimulation.

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“…Penile NOS activity and content were reduced in rat models of both type I and II diabetes with ED (Vernet et al, 1995). However, in rats with streptozotocin-induced diabetes, NOS binding increased (Sullivan et al, 1996), and NOS activity in penile tissue was significantly higher than in control rats, despite a significant degradation of mating behavior and indications of defective erectile potency (Elabbady et al, 1995). In humans, diabetic ED was suggested to be related to the effects of advanced glycation end products on NO formation (Seftel et al, 1997).…”

Section: A Risk Factors and Conditions Associated With Erectile Dysfmentioning

confidence: 99%

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

2011

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Autoradiographic Localization of Nitric Oxide Synthase Binding Sites in Normal and Diabetic Rat Corpus Cavernosum

Cited by 31 publications

References 21 publications

Effects of diabetes and treatment with the antioxidant α-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats

Effects of diabetes and treatment with the antioxidant α-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats

Endothelial and neuronal-derived nitric oxide mediated relaxation of corpus cavernosal smooth muscle in a rat, in vitro, model of erectile function

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

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