Computerized Analysis of Smooth Muscle Fibers in Potent and Impotent Patients

Wespes, Eric; Góes, Patrícia Freitas; Schiffmann, Serge N.; Depierreux, Michel; Vanderhaeghen, Jean‐Jacques; Schulman, Claude

doi:10.1016/s0022-5347(17)37990-9

Cited by 146 publications

(99 citation statements)

References 12 publications

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“…The nucleus is stained blue (DAPI). Negative controls were performed by primary antibody omission (d, h) Aging also leads to change of the cavernous tissue structure (Ferrer et al 2010;Luo et al 2007;Tomada et al 2008Tomada et al , 2010bWespes et al 1991) and, despite the controversy of reports concerning SM and CT content, such changes seem to be one of multiple contributing factors for the age-dependent erectile dysfunction (El-Sakka and Yassin 2010;Yassin and Saad 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, dilation of the resistance arterial bed of the penis favors blood flow and entrapment in the corpus cavernosum (CC), a combined effect of expansion of the lacunar spaces by relaxation of the trabecular smooth muscle (SM) and compression of the draining venules. The efficiency of this process strongly depends on the integrity of the trabecular SM as corpora expansion is related directly to its content and inversely to that of connective tissue (CT) (Luo et al 2007;Nehra et al 1996;Wespes et al 1991). In fact, cavernous SM cell loss or functional impairment is the etiological basis of erectile dysfunction (ED) in many patients, since muscular tonus regulates the stages of erection, which cannot be achieved by vascular mechanisms alone (Wespes 2002).…”

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confidence: 99%

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Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Tomada

Almeida

et al. 2011

AGE

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Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD + -dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Tomada

Almeida

et al. 2011

AGE

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“…Some of these changes are considered as the result of the aging process and others correspond to pathological modifications probably due to certain diseases or specific risk factors related to the vascular system. [21][22][23] In extracavernosal segments of the vascular bed, the tone and contractility of VSM and, then, the modulation of regional blood Candesartan and cavernous tissue in SHR JE Toblli et al flow depend on a balance between angiotensin II and NO. [24][25][26] There is compelling evidence supporting that corpus cavernous produces and secretes physiologically relevant amounts of angiotensin II and that the local renin-angiotensin system is involved in the regulation of CSM tone through angiotensin II receptor subtype 1.…”

Section: Discussionmentioning

confidence: 99%

Candesartan cilexetil protects cavernous tissue in spontaneously hypertensive rats

Toblli

Stella²,

Mazza

et al. 2004

Int J Impot Res

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In previous experiments, our group demonstrated morphological changes in erectile tissue from male spontaneously hypertensive rats (SHR). The present study was performed to determine whether an angiotensin II receptor blocker could protect cavernous tissue (CT) from these structural alterations in SHR. Male SHR and Wistar-Kyoto (WKY) rats were studied during 4 months. Rats were divided into three groups: SHR (n ¼ 10), SHR with candesartan cilexetil (n ¼ 10) and WKY rats (n ¼ 10). Candesartan cilexetil 7.5 mg/kg/day was administered orally throughout the study. CT was processed for pathology studies. The amount of (1) cavernous smooth muscle (CSM), (2) vascular smooth muscle (VSM), (3) collagen type III, and the rat endothelial cell antibody (RECA-1)/tunica media ratio in cavernous arteries were evaluated. SHR with candesartan cilexetil showed a lower blood pressure, a lower percentage of CSM, smaller VSM area, with a higher RECA-1/media ratio, and a lower percentage of collagen type III, when compared to untreated SHR. In addition, SHR showed a positive correlation between systolic blood pressure (SBP) and CSM amount (r ¼ 0.91; Po0.01), and SBP and the percentage of collagen type III (r ¼ 0.88; Po0.01); these correlations were not observed either in SHR treated with candesartan cilexetil or in WKY rats. We conclude that candesartan cilexetil provides a significant protective role against morphologic changes in vessels as well as in cavernous spaces of the erectile tissue, caused by high blood pressure, in SHR.

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“…Approximately 45% of cavernosal volume is smooth muscle. 1 Regulation of its contractility depends on adequate levels of agonists (neurotransmitters, hormones, and endothelium-derived factors), adequate expression of receptors, integrity of transduction mechanisms, calcium homeostasis, interactions with contractile proteins and intercellular communication between smooth muscle cells (gap junctions). 2 Ultrastructural examination of a smooth muscle cell reveals thin, thick and intermediate filamentous structures.…”

Section: Penile Smooth Musclementioning

confidence: 99%

Molecular mechanisms for the regulation of penile smooth muscle contractility

Tejada¹

2002

Int J Impot Res

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Relaxation of penile smooth muscle (arterial and trabecular) initiates and maintains penile erection. Relaxation of smooth muscle is viewed as a 'resetting' of contractile machinery by resumption of a precontractile state accomplished by lowering cytosolic Ca þ2 and=or by a decrease in sensitivity of the contractile machinery to Ca þ2 . There are various mechanisms whereby cytosolic Ca þ2 can be reduced and relaxation achieved, but in general, all pathways depend on the accumulation of the nucleotides cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) or activation of K channels with hyperpolarization. Another mechanism, activation of Na þ =K þ adenosine triphosphatase (ATPase) by nitric oxide, has been shown to be involved in relaxation of trabecular smooth muscle. Since Na þ =K þ ATPase is electrogenic, its stimulation would cause hyperpolarization. Hyperpolarization will prevent the opening of voltage-dependent calcium channels. Guanylate cyclase, which catalyzes the conversion of guanosine triphosphate to cGMP, is activated by nitric oxide. cGMP activates protein kinase G, which through multiple phosphorylations facilitates calcium sequestration and reduces the entry of calcium into the cell. Other muscle relaxants act by way of a cAMP-dependent mechanism such as prostaglandin E, vasoactive intestinal polypeptide, and catecholamines (via breceptors). These substances react with membrane receptors coupled to a GS-type protein that stimulates adenylate cyclase, which catalyzes the accumulation of cAMP. International Journal of Impotence Research (2002) 14, Suppl 1, S6-S10. DOI: 10.1038= sj=ijir=3900790Keywords: erectile dysfunction; penile erection; penile smooth muscle contractility Penile smooth muscleThe smooth muscle of the penis is a key determinant of the hemodynamic events that govern penile erection. Approximately 45% of cavernosal volume is smooth muscle. 1 Regulation of its contractility depends on adequate levels of agonists (neurotransmitters, hormones, and endothelium-derived factors), adequate expression of receptors, integrity of transduction mechanisms, calcium homeostasis, interactions with contractile proteins and intercellular communication between smooth muscle cells (gap junctions). 2 Ultrastructural examination of a smooth muscle cell reveals thin, thick and intermediate filamentous structures. 2 Thin filaments are mainly composed of actin. Thick filaments are formed of myosin. Intermediate filaments contain either desmin or vimentin. Each type of filament has a specific function.Following phosphorylation of myosin by adenosine triphosphate (ATP), attachments form between the globular heads of a light chain of myosin and actin. These attachments are known as cross-bridges and provide a contractile tone to the smooth muscle. 3 For the maintenance of this tone, there is a near-zero expenditure of energy, in other words, ATP for myosin phosphorylation. This prolonged maintenance of tone has been attributed to the formation of a latch state during which cross-brid...

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Computerized Analysis of Smooth Muscle Fibers in Potent and Impotent Patients

Cited by 146 publications

References 12 publications

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Candesartan cilexetil protects cavernous tissue in spontaneously hypertensive rats

Molecular mechanisms for the regulation of penile smooth muscle contractility

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