Vasopressin-induced mouse urethral contraction is modulated by caveolin-1

Zeng, Jing; Ekman, Mari; Grossi, Mario; Svensson, Daniel; Nilsson, Bengt J.; Jiang, Chonghe; Uvelius, Bengt; Swärd, Karl

doi:10.1016/j.ejphar.2015.01.029

Cited by 12 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It appears likely that vasopressin influences the bladder directly as we observed the same effects of vasopressin in the “pithed” DAPM preparation. It has been noted that vasopressin (via V1a receptors) contracts mouse internal urethral sphincter in vitro . We found higher doses of vasopressin increased phasic EUS‐EMG activity, which might also represent a direct action of vasopressin on the sphincter.…”

Section: Discussionsupporting

confidence: 57%

Characterization of mouse neuro‐urological dynamics in a novel decerebrate arterially perfused mouse (DAPM) preparation

Ito

Drake

Fry

et al. 2018

Neurourology and Urodynamics

View full text Add to dashboard Cite

AimTo develop the decerebrate arterially perfused mouse (DAPM) preparation, a novel voiding model of the lower urinary tract (LUT) that enables in vitro‐like access with in vivo‐like neural connectivity.MethodsAdult male mice were decerebrated and arterially perfused with a carbogenated, Ringer's solution to establish the DAPM. To allow distinction between central and peripheral actions of interventions, experiments were conducted in both the DAPM and in a “pithed” DAPM which has no brainstem or spinal cord control.ResultsFunctional micturition cycles were observed in response to bladder filling. During each void, the bladder showed strong contractions and the external urethral sphincter (EUS) showed bursting activity. Both the frequency and amplitude of non‐voiding contractions (NVCs) in DAPM and putative micromotions (pMM) in pithed DAPM increased with bladder filling. Vasopressin (>400 pM) caused dyssynergy of the LUT resulting in retention in DAPM as it increased tonic EUS activity and basal bladder pressure in a dose‐dependent manner (basal pressure increase also noted in pithed DAPM). Both neuromuscular blockade (vecuronium) and autonomic ganglion blockade (hexamethonium), initially caused incomplete voiding, and both drugs eventually stopped voiding in DAPM. Intravesical acetic acid (0.2%) decreased the micturition interval. Recordings from the pelvic nerve in the pithed DAPM showed bladder distention‐induced activity in the non‐noxious range which was associated with pMM.ConclusionsThis study demonstrates the utility of the DAPM which allows a detailed characterization of LUT function in mice.

show abstract

Section: Discussionsupporting

confidence: 57%

Characterization of mouse neuro‐urological dynamics in a novel decerebrate arterially perfused mouse (DAPM) preparation

Ito

Drake

Fry

et al. 2018

Neurourology and Urodynamics

View full text Add to dashboard Cite

show abstract

“…Female outflow tracts were instead contracted with AVP to enable relaxation to be studied, as previously described. 27 In that context, EFS evoked relaxation responses that were frequency-dependent and tetrodotoxin-sensitive in female WT outflow tracts, as seen in males. 23 In addition to reduced relaxation, EFS further evoked an initial paradoxical contraction of Lrig2 mutant female outflows precontracted with AVP, which was absent in WT preparations.…”

Section: Discussionmentioning

confidence: 95%

“… 26 Relaxation was calculated by determining the absolute difference immediately before EFS application to the maximum decrease during stimulation, relative to the stable PE-induced increase in tension (i.e., the “PE baseline”). Because female mouse urethras express transcripts encoding the arginine vasopressin (AVP) V1a receptor, 27 they were instead precontracted with (AVP). In separate experiments, outflow tracts or bladder bodies were stimulated with 50 mM KCl to directly depolarize the smooth muscle, which stimulates Ca 2+ influx through voltage-gated Ca 2+ channels to elicit contraction.…”

Section: Methodsmentioning

confidence: 99%

Neurogenic Defects Occur in LRIG2-Associated Urinary Bladder Disease

Grenier

Lopes

Cueto‐González

et al. 2023

Kidney International Reports

View full text Add to dashboard Cite

“…The α-1 adrenergic receptor agonist, phenylephrine (PE, 1 μM), was therefore used to contract male outflow tracts before applying electrical field stimulation (EFS; 1 ms pulses of 80 V at 0.5–15 Hz for 10 s) to induce nerve-mediated relaxation. Female outflow tracts were instead pre-contracted with vasopressin (10 nM) as previously detailed (Grenier et al , 2023), because they are known to express contractile arginine-vasopressin (AVP) receptors (Zeng et al , 2015). Bladder body rings were subjected to EFS (1 ms pulses of 80V at 0.5–25 Hz for 10 s) to induce frequency-dependent detrusor contractions.…”

Section: Methodsmentioning

confidence: 99%

HumanHPSE2gene transfer ameliorates bladder pathophysiology in a mutant mouse model of urofacial syndrome

Lopes,

Grenier,

Jarvis

et al. 2023

Preprint

View full text Add to dashboard Cite

Rare early onset lower urinary tract disorders include defects of functional maturation of the bladder. Current treatments do not target the primary pathobiology of these diseases. Some have a monogenic basis, such as urofacial, or Ochoa, syndrome (UFS). Here, the bladder does not empty fully because of incomplete relaxation of its outflow tract, and subsequent urosepsis can cause kidney failure. UFS is associated with biallelic variants of HPSE2, encoding heparanase-2. This protein is detected in pelvic ganglia, autonomic relay stations that innervate the bladder and control voiding. Bladder outflow tracts of Hpse2 mutant mice display impaired neurogenic relaxation. We hypothesized that HPSE2 gene transfer soon after birth would ameliorate this defect and explored an adeno-associated viral (AAV) vector-based approach. AAV9/HPSE2, carrying human HPSE2 driven by CAG, was administered intravenously into neonatal mice. In the third postnatal week, transgene transduction and expression were sought, and ex vivo myography was undertaken to measure bladder function. In mice administered AAV9/HPSE2, the transduced genome was detected in pelvic ganglia, where human HPSE2 was also expressed. Moreover, heparanase-2 became detectable in pelvic ganglia of treated mutant mice. On autopsy, untreated mutant mice had distended urinary bladders, consistent with bladder outflow obstruction, but AAV9/HPSE2-administered mice did not, thus resembling wild-type mice. AAV9/HPSE2 significantly ameliorated impaired neurogenic relaxation of Hpse2 mutant bladder outflow tracts. Impaired neurogenic contractility of mutant detrusor smooth muscle was also significantly ameliorated by AAV9/HPSE2. These results constitute first steps towards curing UFS, a clinically devastating genetic disease featuring a bladder autonomic neuropathy.

show abstract

Vasopressin-induced mouse urethral contraction is modulated by caveolin-1

Cited by 12 publications

References 37 publications

Characterization of mouse neuro‐urological dynamics in a novel decerebrate arterially perfused mouse (DAPM) preparation

Characterization of mouse neuro‐urological dynamics in a novel decerebrate arterially perfused mouse (DAPM) preparation

Neurogenic Defects Occur in LRIG2-Associated Urinary Bladder Disease

HumanHPSE2gene transfer ameliorates bladder pathophysiology in a mutant mouse model of urofacial syndrome

Contact Info

Product

Resources

About