Rat Model for the Study of
Penile Erection: Pharmacologic
and Electrical-Stimulation
Parameters

Martínez‐Piñeiro, Luis; Brock, Geoffrey; Trigo-Rocha, Flavio; Hsu, Geng‐Long; Lue, Tom F.; Tanagho, Emil A.

doi:10.1159/000475249

Cited by 60 publications

(31 citation statements)

References 23 publications

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“…Intracavernous pressure response to nerve stimulation is identified to be an index for the quantitative assessment of penile erection in animal models. 18 Thus, the impaired pressure response to preliminary intravenous 11 as well as oral E 2 administration in the present investigation is presumably due to a detrimental effect of oestrogen on neuronal nitric oxide (NO)-mediated response of penile tumescence and rigidity; the mechanism of this action needs further investigation and elucidation.…”

Section: Oestradiolmentioning

confidence: 73%

Oestrogen-mediated hormonal imbalance precipitates erectile dysfunction

Adaikan

Srilatha

2003

Int J Impot Res

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Declining testosterone (T) in an aging male offsets the equilibrium between androgen and oestrogen (oestradiol, E 2 ) with a resultant increase in E 2 -T ratio. Similar functional hormone imbalance is existent in clinical states of hypogonadism and is likely to arise from exposure of males to environmental oestrogens. The pathophysiological significance of this derangement on erectile function, hitherto unknown, was estimated in sexually mature male rats following acute and chronic treatment with oestrogen. A total of 60 male Sprague-Dawley rats (200-250 g) were divided into control and two treatment groups, administered 0.01 and 0.1 mg of oestradiol through oral gavage daily for 1 week (n ¼ 30, acute study) and 12 weeks (n ¼ 30, long-term study), respectively. Sexual activity in the presence of hormonally primed female rats and intracavernous pressure (ICP) response to electrical stimulation estimated treatment-induced changes, which were correlated with hormone levels and penile morphology at 12 weeks. Following two to five-fold elevation in serum E 2 levels (and simultaneous reduction in testosterone), there was a significant prolongation of mount, intromission, ejaculation latencies and some decrease in frequencies. The ICP response to nerve stimulation was also impaired in all the treated groups. Histologically, trichrome staining highlighted the cavernosal connective tissue hyperplasia in the long-term study groups. Results of this investigation indicate that oestradiol causes pathophysiological changes in erectile function. These observations provide an indirect evidence for the possible sexual health hazards in man upon inadvertent exposure to environmental oestrogens, ageing and derangement of E 2 -T ratio.

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Section: Oestradiolmentioning

confidence: 73%

Oestrogen-mediated hormonal imbalance precipitates erectile dysfunction

Adaikan

Srilatha

2003

Int J Impot Res

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“…To determine whether the increase in eNOS phosphorylation elicited by cavernous nerve stimulation is secondary to augmented blood flow, we injected rats with papaverine intracavernosally, a procedure well known to elicit vasorelaxation and to increase ICP in rodents (42), and assessed the phosphorylation state of eNOS-S1177 and Akt-S473 (Table 1). Although papaverine responses are more variable than those after electrical stimulation, papaverine induced phosphorylation of Akt by 40% and of eNOS by 70%, indicating that augmented blood flow and endothelial shear stress may account for increased phosphorylation of penile eNOS.…”

Section: Electrical Stimulation and Pharmacostimulation Elicit Phosphmentioning

confidence: 99%

Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection

Hurt

Musicki

Palese

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

346

277

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In the penis, nitric oxide (NO) can be formed by both neuronal NO synthase and endothelial NOS (eNOS). eNOS is activated by viscous drag͞shear stress in blood vessels to produce NO continuously, a process mediated by the phosphatidylinositol 3-kinase (PI3-kinase)͞Akt pathway. Here we show that PI3-kinase͞Akt physiologically mediates erection. Both electrical stimulation of the cavernous nerve and direct intracavernosal injection of the vasorelaxant drug papaverine cause rapid increases in phosphorylated (activated) Akt and eNOS. Phosphorylation is diminished by wortmannin and LY294002, inhibitors of PI3-kinase, the upstream activator of Akt. The two drugs also reduce erection. Penile erection elicited by papaverine is reduced profoundly in mice with targeted deletion of eNOS. Our findings support a model in which rapid, brief activation of neuronal NOS initiates the erectile process, whereas PI3-kinase͞Akt-dependent phosphorylation and activation of eNOS leads to sustained NO production and maximal erection. N itric oxide (NO) serves many biological functions. As a neurotransmitter, it is produced by neuronal NOS (nNOS). Vascular tone is regulated by NO formed from endothelial NOS (eNOS). Inducible NOS accounts for diverse functions, especially responses to inflammatory stimuli (1-3). A substantial body of evidence implicates NO in normal erectile function: the nerves that regulate penile erection contain nNOS (4-7), NO donors and NOS inhibitors elicit and prevent erection, respectively (8-12), and mice lacking protein kinase G I (PKGI, a major target of NO͞cGMP signaling in the penis) demonstrate a pronounced reduction in reproductive capacity (13).Neurally derived NO is well established as a mediator of smooth muscle cell relaxation in the penis, engorgement of the cavernous sinusoids, and subsequent erection (14,15). eNOS is abundant in the endothelial lining of the penile vessels and trabecular meshwork and is also a potential source of [16][17][18] nNOS and eNOS are activated by calcium entry into the cell, binding to calmodulin associated with the enzymes (22). Whereas physiologic penile erection lasts several minutes, the calcium-dependent activation of nNOS or eNOS is quite transient. Recently, several groups showed that the phosphatidylinositol 3-kinase (PI3-kinase) pathway that activates the serine͞ threonine protein kinase Akt (also known as PKB) causes direct phosphorylation of eNOS, reducing the enzyme's calcium requirement and causing increased production of [23][24][25]. This pathway is responsible for both shear stress and growth-factor enhancement of blood flow that can last for hours (26-30). We have examined whether Akt regulation of eNOS occurs during penile erection and whether that regulation is important in producing and maintaining normal penile erection.We now show that electrical stimulation as well as druginduced relaxation of penile erectile tissue increases phosphorylation and activation of Akt as well as phosphorylation of eNOS. This response is reduced by PI3-kinase inhibitors. Mor...

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“…Through a lower median incision, the lateral prostate was exposed and the cavernous nerve carefully isolated and suspended by platinum wire electrodes (with 1 mm interelectrode distance) for stimulation. 28 A 27 gauge needle ®lled with heparinized saline (250 i.u.aml) was placed in the penile crus (PE 10 tubing) for recording the intracavernous pressure (ICP) response to nerve stimulation. The pressure recordings were obtained at the optimal voltage and frequency of 2 v and 20 hz over 1 ms duration.…”

Section: Cavernous Pressure Evaluationmentioning

confidence: 99%

Sexual dysfunction related to antihypertensive agents: results from the animal model

et al. 1999

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The present investigation elucidates the deleterious effects of three prototypical antihypertensive drugs namely, propranolol, clonidine and captopril on the erectile physiology. In order to delineate the direct drug effects from vascular insuf®ciency inherent in hypertensive states, the study was conducted on a normotensive animal model. The adverse effects of these drugs were estimated as changes in sexual behaviour and intracavernous pressure response to electrical stimulation in the treated rats compared to normal age-matched controls (n 10, each group). Copulation studies indicated signi®cant impairment of sexual function in the groups on propranolol and clonidine. The cavernous pressure response to nerve stimulation at the end of sixteen weeks further reinforced the gross compromise on sexual function in these two treated groups. In contrast, the captopril administration produced only marginal alterations to the responses recorded. The results from this study clearly indicate that propranolol and clonidine interfere with sexual behaviour and nerve mediated response to erection whereas captopril which is devoid of signi®cant effects on these parameters, may be a better therapeutic option.

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Rat Model for the Study of Penile Erection: Pharmacologic and Electrical-Stimulation Parameters

Cited by 60 publications

References 23 publications

Oestrogen-mediated hormonal imbalance precipitates erectile dysfunction

Oestrogen-mediated hormonal imbalance precipitates erectile dysfunction

Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection

Sexual dysfunction related to antihypertensive agents: results from the animal model

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