SM2+/- male mice are predisposed to develop urinary tract obstruction and hyper contractility of the bladder smooth muscle upon ageing

Chi, Mei; Zhou, Yingbi; Sopariwala, Danesh H.; Periasamy, Muthu

doi:10.1540/jsmr.47.67

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…Results are also conflicting regarding a role of carboxyl terminal isoforms on filament assembly (29;30;57). A recent study using SM2 knockout mice shows SM (+/−) male mice with relatively high ratio of SM1/SM2 are predisposed to develop urinary tract obstruction and hypercontractility of bladder smooth muscle upon aging (56). Thus, there is evidence that suggests a relationship between changes in MHC isoform expression and smooth muscle function in this study.…”

Section: Discussionsupporting

confidence: 56%

Effect of estrogen on molecular and functional characteristics of the rodent vaginal muscularis

et al. 2012

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Introduction-Vaginal atrophy is a consequence of menopause however little is known concerning the effect of a decrease in systemic estrogen on vaginal smooth muscle structure and function. As the incidence of pelvic floor disorders increases with age, it is important to determine if estrogen regulates the molecular composition and contractility of the vaginal muscularis.Aim-The goal of this study was to determine the effect of estrogen on molecular and functional characteristics of the vaginal muscularis utilizing a rodent model of surgical menopause.Methods-3-4 month old Sprague Dawley rats underwent sham laparotomy (Sham, n=18) or ovariectomy (Ovx, n=39). Two weeks following surgery, animals received a subcutaneous osmotic pump containing vehicle (Sham, Ovx) or 17-β estradiol (Ovx). Animals were euthanized one week later and the proximal vagina was collected for analysis of contractile protein expression and in vitro studies of contractility. Measurements were analyzed using a one-way ANOVA followed by Tukey's post hoc analysis (α= 0.05). Main Outcome Measures-Protein and mRNA transcript expression levels of contractile proteins, in vitro measurements of vaginal contractilityResults-Ovariectomy decreased the expression of carboxyl-terminal myosin heavy chain isoform SM1 and h-caldesmon and reduced the amplitude of contraction of the vaginal muscularis in response to KCl. Estradiol replacement reversed these changes. No differences were detected in the % vaginal muscularis, mRNA transcript expression of amino terminal MHC isoforms, lcaldesmon expression and maximal velocity of shortening. Conclusion-Systemic estrogen replacement restores functional and molecular characteristics of the vaginal muscularis of ovariectomized rats. Our results indicate that menopause is associated

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Section: Discussionsupporting

confidence: 56%

Effect of estrogen on molecular and functional characteristics of the rodent vaginal muscularis

et al. 2012

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“…Results are also conflicting regarding a role of carboxyl-terminal isoforms on filament assembly [29,30,59]. A recent study using SM2 knockout mice shows SM (+/-) male mice with relatively high ratio of SM1/SM2 are predisposed to develop urinary tract obstruction and hypercontractility of bladder smooth muscle upon aging [58]. Thus, there is evidence that suggests a relationship between changes in MHC isoform expression and smooth muscle function in this study.…”

Section: Discussionmentioning

confidence: 61%

“…Alterations in smooth muscle carboxyl‐terminal isoform expression have also been reported in animal models of bladder outlet obstruction , diabetes , atherosclerosis , and hypertension . Despite reports of changes in carboxyl‐terminal isoform expression in both physiological and pathological conditions, the physiological relevance of the relative expression of SM1/SM2 isoforms is unresolved . Some , but not all , studies have demonstrated a positive correlation between the SM1 isoform and unloaded shortening velocity.…”

Section: Discussionmentioning

confidence: 99%

Effect of Estrogen on Molecular and Functional Characteristics of the Rodent Vaginal Muscularis

Basha

Chang

Burrows

et al. 2013

The Journal of Sexual Medicine

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Introduction Vaginal atrophy is a consequence of menopause however little is known concerning the effect of a decrease in systemic estrogen on vaginal smooth muscle structure and function. As the incidence of pelvic floor disorders increases with age, it is important to determine if estrogen regulates the molecular composition and contractility of the vaginal muscularis. Aim The goal of this study was to determine the effect of estrogen on molecular and functional characteristics of the vaginal muscularis utilizing a rodent model of surgical menopause. Methods 3–4 month old Sprague Dawley rats underwent sham laparotomy (Sham, n=18) or ovariectomy (Ovx, n=39). Two weeks following surgery, animals received a subcutaneous osmotic pump containing vehicle (Sham, Ovx) or 17- β estradiol (Ovx). Animals were euthanized one week later and the proximal vagina was collected for analysis of contractile protein expression and in vitro studies of contractility. Measurements were analyzed using a one-way ANOVA followed by Tukey's post hoc analysis (α= 0.05). Main Outcome Measures Protein and mRNA transcript expression levels of contractile proteins, in vitro measurements of vaginal contractility Results Ovariectomy decreased the expression of carboxyl-terminal myosin heavy chain isoform SM1 and h-caldesmon and reduced the amplitude of contraction of the vaginal muscularis in response to KCl. Estradiol replacement reversed these changes. No differences were detected in the % vaginal muscularis, mRNA transcript expression of amino terminal MHC isoforms, l-caldesmon expression and maximal velocity of shortening. Conclusion Systemic estrogen replacement restores functional and molecular characteristics of the vaginal muscularis of ovariectomized rats. Our results indicate that menopause is associated with changes in the vaginal muscularis, which may contribute to the increased incidence of pelvic floor disorders with age.

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“…In support of this hypothesis, mice that have reduced levels of smooth muscle myosin isoforms SM1 and SM2 (SM2 +/- mice) exhibit a bladder phenotype that is strikingly similar to that of Mras -/- mice. About half of SM2 +/- males exhibit bladder distension at 18 months of age, and the detrusor is hypersensitive to both K + depolarization and carbachol stimulation [ 61 ]. Thus, it is tempting to speculate that M-Ras might dampen smooth muscle contractility by negatively affecting smooth muscle actin (SMA) polymerization.…”

Section: Discussionmentioning

confidence: 99%

Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras

et al. 2015

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Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras -/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly ‘layered’ with age in Mras -/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras -/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras -/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras -/- males were increased, and Mras -/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras -/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice.

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SM2+/- male mice are predisposed to develop urinary tract obstruction and hyper contractility of the bladder smooth muscle upon ageing

Cited by 5 publications

References 27 publications

Effect of estrogen on molecular and functional characteristics of the rodent vaginal muscularis

Effect of estrogen on molecular and functional characteristics of the rodent vaginal muscularis

Effect of Estrogen on Molecular and Functional Characteristics of the Rodent Vaginal Muscularis

Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras

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