Age-dependent Alterations in beta-adrenergic Responsiveness of Rat Detrusor Smooth Muscle

Nishimoto, Tadashi; Latifpour, Jamshid; Wheeler, Marcia A.; Yoshida, Masaki; Weiß, Robert M.

doi:10.1016/s0022-5347(01)67508-6

Cited by 56 publications

(33 citation statements)

References 14 publications

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“…Although a number of studies have been published on age-related changes in bladder function, no consensus has been reached [1][2][3][4][5][6][7][8][9]. Chun et al [3] observed that, in the in vivo rat bladder, both the total micturition volume and the frequency of micturition are significantly greater in old than young rats.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Ageing on Blood Flow to the Bladder and Bladder Function

Saito

Ohmura²,

Kondo³

1999

Urol Int

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Ischemia, induced by atherosclerosis, is a common cause of disorders in the elderly. Bladder dysfunction in older people may be caused by detrusor ischemia. We compared blood flow to the bladder and detrusor function in vivo and in vitro in young (6-month-old) and aged (24-month-old) male Sprague-Dawley rats. In both young and old rats, blood flow to the bladder measured by a laser Doppler flowmeter decreased as intravesical volume increased and was smaller in old rats than in young rats. Cystometrograms performed under anesthesia showed that old rats had smaller voiding pressure and larger bladder capacity than young rats. In isolated bladders, the pressure increase in response to bethanechol and low frequency field stimulation were impaired by aging. Volume-pressure studies showed that in isolated bladders of old rats compliance was greater and peak response to field stimulation was observed at a larger capacity. These findings indicate that bladders of older rats have a larger capacity with good compliance, but less contractility. Aging changes correlate with a decrease in blood flow to the bladder.

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Section: Discussionmentioning

confidence: 99%

“…Previous investigations have suggested that the aging process alters micturition dynamics in vivo and contractile strength in vitro in response to some neurotransmitters [1][2][3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Effect of Ageing on Blood Flow to the Bladder and Bladder Function

Saito

Ohmura²,

Kondo³

1999

Urol Int

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“…Bladder strips from OVX and old rats exhibit decreased responsiveness to cholinergic stimulation (Diep and Constantinou, 1999), decreased tetrodotoxin-sensitive ACh release from nerve fibers, and increased tetrodotoxin-insensitive basal and stretchevoked ACh release from the urothelium (Yoshida et al, 2007). Other studies demonstrated hormonal-and/or agerelated alterations in G proteins, ␤AR density, and/or ␤AR responsiveness (Nishimoto et al, 1995;Derweesh et al, 2000;Frazier et al, 2006). Increased levels of G i protein, which inhibits cAMP production, were suggested as an underlying mechanism for the decreased ␤AR-induced relaxation of the bladder in old (24 months) male Fisher 344 rats (Derweesh et al, 2000).…”

Section: ϫ12mentioning

confidence: 98%

“…Increased levels of G i protein, which inhibits cAMP production, were suggested as an underlying mechanism for the decreased ␤AR-induced relaxation of the bladder in old (24 months) male Fisher 344 rats (Derweesh et al, 2000). Bladder strips from old (Ͼ22 months) Fisher 344 (Nishimoto et al, 1995;Derweesh et al, 2000) or Wistar (Frazier et al, 2006) male rats were less relaxed by the nonselective ␤AR agonists isoproterenol or norepinephrine and by the selective ␤ 3 AR agonists (BRL37344 and CGP12177) than bladder strips from young rats. However, other studies found no change in isoproterenol or norepinephrine-induced relaxation of bladder strips from 10-and 30-month-old female Wistar/Rij rats (Lluel et al, 2000).…”

Section: ϫ12mentioning

confidence: 99%

Effects of β3-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Kullmann¹,

Limberg²,

Artim³

et al. 2009

The Journal of Pharmacology and Experimental Therapeutics

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Voiding dysfunctions, including increased voiding frequency, urgency, or incontinence, are prevalent in the postmenopausal population. ␤ 3 -Adrenergic receptor (␤ 3 AR) agonists, which relax bladder smooth muscle, are being developed to treat these conditions. We utilized the rat ovariectomy (OVX) model to investigate the effect of ovarian hormone depletion on bladder function and the potential for ␤ 3 AR agonists to treat bladder hyperactivity in this setting. OVX increased voiding frequency and decreased bladder capacity by ϳ25% in awake rats and induced irregular cystometrograms in urethane-anesthetized rats. Reverse transcription-polymerase chain reaction revealed three ␤ARs subtypes (␤ 1,2,3 ) in bladder tissue, and immunostaining indicated ␤ 3 AR localization in urothelium and detrusor. Receptor expression was not different in OVX and SHAM rats. ]amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]oxy], ethyl ester, hydrochloride] was confirmed by examining the relative potency for elevation of cAMP in CHOK1 cells overexpressing the various rat ␤ARs. Intravenous injection of each of the ␤ 3 AR agonists (0.1-500 g/kg) in anesthetized rats decreased voiding frequency, bladder pressure, and amplitude of bladder contractions. In bladder strips, ␤ 3 AR agonists (10 Ϫ12-10 Ϫ4 M) decreased baseline tone and reduced spontaneous contractions. BRL37344 (5 mg/kg) and TAK-677 (5 mg/kg) injected intraperitoneally in awake rats decreased voiding frequency by 40 to 70%. These effects were not altered by OVX. The results indicate that OVX-induced bladder dysfunction, including decreased bladder capacity and increased voiding frequency, is not associated with changes in ␤ 3 AR expression or the bladder inhibitory effects of ␤ 3 AR agonists. This suggests that ␤ 3 AR agonists should prove effective for the treatment of overactive bladder symptoms in the postmenopausal population.Lower urinary tract (LUT) dysfunctions, including increased voiding frequency, urgency, incontinence and nocturia, increase in the elderly population and following menopause (Stewart et al., 2003). These dysfunctions could result from hormonally induced changes in bladder contractile and/or relaxing mechanisms. Bladder contractions are triggered by parasympathetic nerves, which release ACh that in turn activates postjunctional muscarinic receptors (mAChRs) in the detrusor. Bladder relaxation is induced by release of norepinephrine from sympathetic nerves, which activates ␤-adrenergic receptors (␤AR) (Fowler et al., 2008

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“…In contrast, there are some reports of age-related changes of the detrusor response to adrenergic stimulation (373). Some studies show that detrusor contractile responses to norepinephrine are increased in old male and female rats (473,531,532). Aged female rats also exhibit increases in expression of α 1D -adrenoceptors and α 1D -receptormediated contractions of the bladder (193).…”

Section: Agingmentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

2009

Encyclopedia of Neuroscience

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This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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Age-dependent Alterations in beta-adrenergic Responsiveness of Rat Detrusor Smooth Muscle

Cited by 56 publications

References 14 publications

Effect of Ageing on Blood Flow to the Bladder and Bladder Function

Effect of Ageing on Blood Flow to the Bladder and Bladder Function

Effects of β3-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Neural Control of the Lower Urinary Tract

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