Contractile responses to α<sub>1</sub>‐adrenoceptor agonists in isolated human male and female urethra

Nishimatsu,; Moriyama,; Hamada,; Ukai,; Yamazaki,; Kameyama,; Konno,; Ishida, Toru; Ishii,; Murayama,; Kitamura,

doi:10.1046/j.1464-410x.1999.00218.x

Cited by 16 publications

(10 citation statements)

References 13 publications

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“…Activity in pudendal nerve parasympathetic fibres relaxes urethral smooth muscle, especially in the proximal portion, and therefore the outflow region; hypogastric sympathetic fibres (T10-L2) generate contraction. Symapthetic control is mediated by α 1 receptors, mainly the α 1A/L subtype (Nishimatsu et al, 1999;Bagot and Chess-Williams, 2006) and about half of the urethral pressure is maintained by adrenergic receptor activation (Andersson and Wein, 2004). Partial α 1A/L agonists, such as Ro 115-1240, have been proposed as agents that could manage stress urinary incontinence without significant cardiovascular side-effects (Musselman et al, 2004).…”

Section: Muscles Of the Urethramentioning

confidence: 99%

The physiological function of lower urinary tract smooth muscle

Fry

Meng

Young

2010

Autonomic Neuroscience

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Section: Muscles Of the Urethramentioning

confidence: 99%

The physiological function of lower urinary tract smooth muscle

Fry

Meng

Young

2010

Autonomic Neuroscience

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“…Phenylpropanolamine can inhibit the neuronal uptake of norepinephrine, although this property plays only a minor role in its cardiovascular effects (Hricik and Johnson, 1996). Phenylpropanolamine binds to all three subtypes of ␣ 1 -adrenoceptors (␣ 1A , ␣ 1B , and ␣ 1D ) with relatively low affinity (Buckner et al, 2002) and functions as a low-efficacy agonist at these receptors (Minneman et al, 1983;Minneman and Johnson, 1984;Fox et al, 1985;Alberts et al, 1999;Nishimatsu et al, 1999;Buckner et al, 2002). It has minimal activity at ␤-adrenoceptors (MoyaHuff and Maher, 1987;Hull et al, 1993) and is therefore considered a selective ␣-adrenergic agonist.…”

Section: Introductionmentioning

confidence: 99%

“…In smooth muscle preparations replete with ␣ 1A (human, pig, and rabbit urethra; rat vas deferens) or ␣ 1B -adrenoceptors (rat spleen; rabbit aorta), phenylpropanolamine caused contraction with maximums of 13 to 60% (compared with high-efficacy ␣-adrenergic agonists) and with ED 50 values exceeding ϳ10 Ϫ4 M (Minneman et al, 1983;Fox et al, 1985;Alberts et al, 1999;Nishimatsu et al, 1999;Buckner et al, 2002;Dillon et al, 2004). In rat aorta, which is replete with ␣ 1D -adrenoceptors, phenylpropanolamine was slightly more effective (maximum, 87%; ED 50 value, 6 ϫ 10 Ϫ5 M) (Buckner et al, 2002).…”

mentioning

confidence: 99%

“…However, previous analyses of smooth muscle contraction were generally restricted to preparations that lacked functional ␣ 2 -adrenoceptors (human, pig, or rabbit urethra; rat vas deferens; rat spleen; rat or rabbit aorta; Minneman et al, 1983;Fox et al, 1985;Alberts et al, 1999;Nishimatsu et al, 1999;Buckner et al, 2002;Dillon et al, 2004). Furthermore, when phenylpropanolamine was analyzed in systems expressing ␣ 1 and ␣ 2 -adrenoceptors, the selected responses were restricted to ␣ 1 -adrenoceptors (Minneman and Johnson, 1984;Fox et al, 1985) dominated by ␣ 1 -adrenoceptors (Wellman and Davies, 1991;Wellman and Davies, 1992) or not characterized with regard to ␣-adrenergic subtypes (Stevens and Moulds, 1981).…”

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confidence: 99%

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Phenylpropanolamine Constricts Mouse and Human Blood Vessels by Preferentially Activating α2-Adrenoceptors

Flavahan¹

2004

J Pharmacol Exp Ther

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Phenylpropanolamine (dl-norephedrine) was one of the most widely used therapeutic agents to act on the sympathetic nervous system. Because of concerns regarding incidents of stroke, its use as a nasal decongestant was discontinued. Although considered an ␣ 1 -adrenergic agonist, the vascular adrenergic pharmacology of phenylpropanolamine was not fully characterized. Unlike most other circulations, the vasculature of the nasal mucosa is highly enriched with constrictor ␣ 2 -adrenoceptors. Therefore, experiments were performed to determine whether phenylpropanolamine activates vascular ␣ 2 -adrenoceptors. Mouse tail and mesenteric small arteries and human small dermal veins were isolated and analyzed in a perfusion myograph. The selective ␣ 1 -adrenergic agonist phenylephrine caused constriction of tail and mesenteric arteries and human veins. The selective ␣ 2 -adrenergic agonist UK14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine] caused constriction in tail arteries and in human veins, but not mesenteric arteries. The lack of constriction to UK14,304 was also observed in endothelium-denuded mesenteric arteries. Phenylpropanolamine constricted both types of artery but was 62-fold more potent in tail arteries. In mesenteric arteries, constriction to phenylpropanolamine was not affected by the selective ␣ 2 -adrenergic antagonist, rauwolscine (10 Ϫ7 M) but was abolished by the selective ␣ 1 -adrenergic antagonist, prazosin (3 ϫ 10 Ϫ7 M). In contrast, constriction to phenylpropanolamine in tail arteries and in human veins was inhibited by rauwolscine but not prazosin. Therefore, phenylpropanolamine is a preferential ␣ 2 -adrenergic agonist. At low concentrations, it constricts blood vessels that express functional ␣ 2 -adrenoceptors, whereas at much higher concentrations, phenylpropanolamine also activates vascular ␣ 1 -adrenoceptors. This action likely contributed to phenylpropanolamine's therapeutic activity, namely constriction of the nasal vasculature.Phenylpropanolamine (dl-norephedrine) was one of the most widely used therapeutic agents to act by modulating the sympathetic nervous system. First synthesized in 1912, phenylpropanolamine was introduced as a nasal decongestant in the 1930s (Lasanga, 1988). Its therapeutic use, therefore, predated major discoveries in sympathetic neurophysiology, including the identification of the neurotransmitter norepinephrine (von Euler, 1946, cited in Lasanga, 1988, and the concept of adrenoceptors (Ahlquist, 1948, cited in Lasanga, 1988. Because of concerns regarding episodes of stroke in individuals ingesting phenylpropanolamine, it was withdrawn as a therapeutic agent in 2000 (Kernan et al., 2000).An early report suggested that phenylpropanolamine may possess a cardiac-specific, indirect activity to release norepinephrine from sympathetic nerves (Trendelenburg et al., 1962). However, subsequent studies demonstrated that the cardiovascular effects of phenylpropanolamine result from direct activation of adrenoceptors (e.g., Moya-Huff and Maher, 1987...

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“…21 In the proximal female urethra, the expression of α 1 -adrenoceptor subtype mRNA has a reported ratio of 90:0:10 for α 1A , α 1B and α 1D , respectively. 22 However, Nishimatsu and colleagues 23 reported that phenylephrine, a nonselective α 1 -adrenoceptor agonist, induced contractions through the α 1L receptor, and not through the α 1A subtype. The role of each of these α 1 -adrenoceptor subtypes in relation to urethral contractile function has yet to be delineated.…”

Section: Discussionmentioning

confidence: 99%

Effect of extended-term estrogen on voiding in a postpartum ovariectomized rat model

Hayashi

Bella

Wang

et al. 2012

CUAJ

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Introduction:We tested the hypothesis that extended-term (5-week) estrogen therapy would negatively impact voiding function in a postpartum, ovariectomized rat model. Methods:Immediately after delivery, 30 primiparous Sprague-Dawley rats underwent intravaginal balloon dilation, followed by ovariectomy 1 week later. Cystometry at postpartum week 2 determined normal or abnormal voiding patterns. After randomization, one-half the normal and abnormal voiding rats received 5 weeks of estrogen therapy, while the remainder received placebo. Estrogen effect was determined by repeat cystometry and immunohistochemical analysis of the urethra and vagina.Results: Abnormal voiding increased from 60.0% to 73.3% in the estrogentreated group and declined from 60% to 33% for the placebo group. Rats were then divided into 4 groups for comparison: normal voiding versus placebo (group 1), abnormal voiding versus placebo (group 2), normal voiding versus estrogen (group 3) and abnormal voiding versus estrogen (group 4). Bladder capacity, leak point pressure and maximum voiding pressure were most depressed in group 4. Estrogen treatment was associated with a significant downregulation of α 1A and α 1D -adrenoceptors in the urethral submucosa but an upregulation of nNOS in the urethral smooth muscle. Conclusion:Extended-term estrogen therapy in a rat model of simulated birth trauma and ovariectomy resulted in a higher rate of incontinence. Immunohistochemical examination demonstrated significant downregulation of urethral α 1A -and α 1D -adrenoceptors and upregulation of neuronal nitric oxide synthase (nNOS) in the urethra of estrogen-treated groups. These studies question the use of hormone replacement therapy in the treatment of postmenopausal incontinence.

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Contractile responses to α₁‐adrenoceptor agonists in isolated human male and female urethra

Cited by 16 publications

References 13 publications

The physiological function of lower urinary tract smooth muscle

The physiological function of lower urinary tract smooth muscle

Phenylpropanolamine Constricts Mouse and Human Blood Vessels by Preferentially Activating α2-Adrenoceptors

Effect of extended-term estrogen on voiding in a postpartum ovariectomized rat model

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Contractile responses to α1‐adrenoceptor agonists in isolated human male and female urethra

Cited by 16 publications

References 13 publications

The physiological function of lower urinary tract smooth muscle

The physiological function of lower urinary tract smooth muscle

Phenylpropanolamine Constricts Mouse and Human Blood Vessels by Preferentially Activating α2-Adrenoceptors

Effect of extended-term estrogen on voiding in a postpartum ovariectomized rat model

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Contractile responses to α₁‐adrenoceptor agonists in isolated human male and female urethra