SILDENAFIL, A TYPE-5 CGMP PHOSPHODIESTERASE INHIBITOR, SPECIFICALLY AMPLIFIES ENDOGENOUS cGMP-DEPENDENT RELAXATION IN RABBIT CORPUS CAVERNOSUM SMOOTH MUSCLE IN VITRO

Chuang, Alex T.; Strauss, John D.; Murphy, Richard A.; Steers, William D.

doi:10.1097/00005392-199807000-00094

Cited by 15 publications

(16 citation statements)

References 17 publications

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“…Sildenafil is a well-known PDE 5 inhibitor; it inhibits the inactivation of cGMP which causes relaxation of corpus cavernosum and hence erection (Chuang et al, 1998). Sildenafil was also shown to act as an alpha-blocker and direct potassium channel opener (El-Metwally et al, 2007).…”

Section: Groupmentioning

confidence: 99%

Evaluation of vitamin E in the treatment of erectile dysfunction in aged rats

Helmy

Senbel

2012

Life Sciences

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Section: Groupmentioning

confidence: 99%

Evaluation of vitamin E in the treatment of erectile dysfunction in aged rats

Helmy

Senbel

2012

Life Sciences

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“…During male sexual arousal, activation of NANC nerves results in the synthesis and release of NO, which diffuses into the trabecular smooth muscle, stimulates trabecular smooth muscle-soluble guanylatecyclase (sGC) and increases the synthesis of the intracellular second messenger cyclic guanosine monophosphate (cGMP), resulting in an increased intracellular cGMP concentration [20]. The NO/cGMP signal-transduction pathway integrates into the overall regulation of intracellular calcium concentration, resulting in reduced intracellular calcium by subcellular sequestration or by extrusion, ultimately decreasing smooth muscle tone and thereby enhancing relaxation and penile erection [24]. The concentration of intracellular Ca 2+ is critical for penile smooth muscle relaxation.…”

Section: Pathophysiology Of Erectionmentioning

confidence: 99%

Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction

Aversa¹,

Bruzziches²,

Pili³

et al. 2006

CPD

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Erectile dysfunction (ED) has multifactor pathogenesis, with neurological, vascular, endocrinological and psychogenic components described. However, about 50-85% of ED population report the presence of one or more comorbidities i.e. hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair endothelial function and, erection is a basically vascular event that necessitates an intact endothelium to occur. Hence, ED may be mostly considered as the clinical manifestation of a disease affecting penile circulation as a part of a generalized vascular disorder due to atherosclerosis. Orally active drugs, i.e. phosphodiesterase type-5 inhibitors (PDE5-i), are a group of on-demand drugs licensed for ED treatment and appear to offer advantages over past therapies in terms of ease of administration and cost, and they are now widely advocated as first-line therapy. The recent discovery that chronic not on-demand administration of these drugs may improve erectile and endothelial response in men previously unresponding to on-demand regimes, opens a new scenario in the treatment of men with ED and comorbidities. Finally, the recent approval of PDE5-i sildenafil for the treatment of pulmonary arterial hypertension represents the new challenge for these class of drugs. Aim of this article will be to provide an update on the pathophysiology of ED and how to use of different available PDE5-i in approaching sexual dysfunctional men, pointing out on their characteristic of efficacy and safety and different indications in special sub-populations.

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“…Sildenafil is highly selective for PDE 5 [98], and has been found to have clinical efficacy in the treatment of male impotence following oral administration [99, 100]. By inhibition of PDE 5 sildenafil increases smooth muscle cGMP content in erectile smooth muscle leading to an enhanced duration of NO-mediated relaxation of isolated corpus cavernosum smooth muscle and penile arteries [76, 98, 101]. In isolated penile arteries sildenafil inhibits contractions induced by electrical field stimulation [76, 102], but this is not the case for preparations incubated with an inhibitor of NOS [76].…”

Section: Penile Vasorelaxation and Erectionmentioning

confidence: 99%

Penile Arteries and Erection

Simonsen

García‐Sacristán²,

Prieto³

2002

J Vasc Res

101

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Alterations in the flow of blood to and from the penis are thought to be the most frequent causes of male erectile dysfunction and, therefore, the present review focuses on the penile vasculature. In the flaccid state, tonic noradrenaline release from the sympathetic nerves contracts penile arterial and corporal smooth muscle through activation of postjunctional α₁-adrenoceptors, both by increasing intracellular calcium and by enhancing the sensitivity of the contractile apparatus for calcium. In addition, noradrenaline inhibits vasodilatatory neurotransmitter release by prejunctional α₂-adrenoceptors. The exact role of the sympathetic neurotransmitters, neuropeptide Y and adenosine 5′-triphosphate, in erection is largely unknown. Penile vasodilatation during erection is mediated by nitric oxide (NO) through activation of guanylyl cyclase in the smooth muscle layer, followed by increases in cyclic guanosine monophosphate lowering of intracellular calcium and desensitisation of the contractile apparatus for calcium. Acetylcholine, vasoactive intestinal peptide as well as peptides in sensory nerves probably also play a role in penile vasodilation. Increased flow through the penile arteries stimulates the endothelium leading to release of NO, prostanoids and a non-NO non-prostanoid factor, and as such enhances the vasodilatation, while the role of endothelium-derived contractile factors in penile vasoconstriction is not clear. Erectile dysfunction shares arterial risk factors with ischaemic heart disease, and diabetes, age, and hypercholesterolaemia are associated with impairment of both neurogenic and endothelium-dependent vasodilator mechanisms in corpus cavernosum. Only few studies have investigated the impact of these risk factors on the penile vasculature, although recent evidence suggests that arterial insufficiency precedes changes in corpus cavernosum leading to erectile dysfunction.

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SILDENAFIL, A TYPE-5 CGMP PHOSPHODIESTERASE INHIBITOR, SPECIFICALLY AMPLIFIES ENDOGENOUS cGMP-DEPENDENT RELAXATION IN RABBIT CORPUS CAVERNOSUM SMOOTH MUSCLE IN VITRO

Abstract: Sildenafil relaxes CCSM by amplifying the effects of the normal, endogenous cGMP dependent relaxation mechanisms.

Cited by 15 publications

References 17 publications

Evaluation of vitamin E in the treatment of erectile dysfunction in aged rats

Evaluation of vitamin E in the treatment of erectile dysfunction in aged rats

Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction

Penile Arteries and Erection

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