Alteration of urothelial‐mediated tone in the ischemic bladder: Role of eicosanoids

Azadzoi, Kazem M.; Heim, Vanessa K.; Tarcan, Tufan; Siroky, Mike B.

doi:10.1002/nau.20029

Cited by 41 publications

(46 citation statements)

References 23 publications

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“…Those other cell types include the endometrium which lies inside the myometrial smooth muscle of the uterus, the enteric nervous system which innervates the intestinal smooth muscle of the duodenum, and the urothelium which separates the detrusor smooth muscle of the bladder wall from the urine inside. But while these nonmuscular cells may be able to modulate spontaneous contractility of the adjacent smooth muscle cell layers (Gershon, 1981;Granger et al, 1986;Haynes and Pennefather, 1993;Buckner et al, 2002;Azadzoi et al, 2004;Bulbul et al, 2007;Kanai et al, 2007), they are not likely the primary site for gemfibrozil's relaxant effects. If, for example, gemfibrozil's relaxation of the duodenal contractility seen in Figure 5 were mediated solely by inhibition of enteric neuronal release of contractile neurotransmitters, then we would not expect to see its relaxant influence in uterus and bladder as well.…”

Section: Effects Of Gemfibrozil On Spontaneous Contractions Of Rat Utmentioning

confidence: 99%

“…uterus, duodenum and bladder. These tissues are known for their ability to exhibit spontaneously-occurring phasic rhythmic contractions, which are physiologically relevant and can be observed in vitro without the need to administer contractile agents (Small and Weston, 1971;Gershon, 1981;Granger et al, 1986;Leroy et al, 1991;Haynes and Pennefather, 1993;Buckner et al, 2002;Vedernikov et al, 2003;Azadzoi et al, 2004;Szigeti et al, 2005;Bulbul et al, 2007;Kanai et al, 2007). We determined if gemfibrozil inhibits these spontaneous activities.…”

Section: Introductionmentioning

confidence: 99%

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Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil

Phelps

Peuler

2010

J. Smooth Muscle Res.

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Fibrates are commonly employed to treat abnormal lipid metabolism via their unique ability to stimulate peroxisome proliferator-activated receptor alpha (PPARα). Interestingly, they also decrease systemic arterial pressure, despite recent evidence that PPARα may contribute to expression of renin and related hypertension. Yet, mechanisms responsible for their potential antihypertensive activity remain unresolved. Rapid decreases in arterial pressure following bolus intravenous injections of bezafibrate strongly suggest they may relax arterial smooth muscle directly. But since bezafibrate is highly susceptible to photodegradation in aqueous media, it has never been critically tested for this possibility in vitro with isolated arterial smooth muscle preparations. Accordingly, we tested gemfibrozil which is resistant to photodegradation. We examined it over a therapeutically-relevant range (50-400 μM) for both acute and delayed relaxant effects on contractions of the isolated rat tail artery; contractions induced by either depolarizing its smooth muscle cell membranes with high potassium or stimulating its membrane-bound receptors with norepinephrine and arginine-vasopressin. We also examined these same gemfibrozil levels for effects on spontaneously-occurring phasic rhythmic contractile activity, typically not seen in arteries under in vitro conditions but commonly exhibited by smooth muscle of uterus, duodenum and bladder. We found that gemfibrozil significantly relaxed all induced forms of contraction in the rat tail artery, acutely at the higher test levels and after a delay of a few hours at the lower test levels. The highest test level of gemfibrozil (400 μM) also completely abolished spontaneously-occurring contractile activity of the isolated uterus and duodenum and markedly suppressed it in the bladder. This is the first evidence that a fibrate drug can directly relax smooth muscle contractions, either induced by various contractile agents or spontaneously-occurring. These findings are particularly relevant to both the recently renewed concern over the impact of fibrates on hypertension and a new understanding of their gastrointestinal side effects.

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Section: Effects Of Gemfibrozil On Spontaneous Contractions Of Rat Utmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil

Phelps

Peuler

2010

J. Smooth Muscle Res.

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“…Ischemia may also increase the release of leukotrienes from the urothelium [47] . Prostaglandins in women [49] and leukotrienes in guinea-pigs [48] were also implicated in bladder contractility changes.…”

Section: Animal Models Of Ischemia-induced Bladder Dysfunctionmentioning

confidence: 99%

“…Materials and Methods: We performed a search on the online database PubMed/MEDLINE with the following MESH terms: 'Overactive Bladder AND (Ischemia OR Aging OR Vascular Disease)'. We considered manuscripts written in English and published in the last 10 years (2004. Additional manuscripts, such as referenced by reviews, were further included.…”

mentioning

confidence: 99%

Lower Urinary Tract Symptoms and Aging: The Impact of Chronic Bladder Ischemia on Overactive Bladder Syndrome

Camões

Coelho²,

Castro-Díaz

et al. 2015

Urol Int

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Introduction: The overactive bladder syndrome (OAB) is one of the most common and bothersome subsets of lower urinary tract symptoms (LUTS), affecting predominantly the aged population, with a worldwide distribution. This syndrome has not been completely understood, yet the aging process and the decreased blood flow to the bladder have been highlighted as closely related to this phenomenon. Materials and Methods: We performed a search on the online database PubMed/MEDLINE with the following MESH terms: ‘Overactive Bladder AND (Ischemia OR Aging OR Vascular Disease)'. We considered manuscripts written in English and published in the last 10 years (2004-2014, October). Additional manuscripts, such as referenced by reviews, were further included. Results: The aging process and the structural and functional changes resulting from an ischemic process emerge as important features that contribute to OAB. The ischemic-induced molecular and structural modifications that occur in the bladder have only recently been the objective of thorough studies, which link cardiovascular risk factors, vascular lesions and OAB. New animal models are being created to test new areas of treatment or prevention of ischemic-induced bladder dysfunction. Conclusion: Recent data point out that several physiological and pathological modifications that occur in the bladder associated with OAB and aging are closely related to ischemia.

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“…These ischemic conditions are considered to affect bladder nerve distribution and detrusor function, resulting in urgency and voiding dysfunction. Ischemic condition in the bladder involves partial denervation and a compensatory increase in nerve growth factor expression [4][5][6] . An increase in nerve growth factor leads to neuronal hypertrophy and bladder nerve sensitization [7,8] .…”

Section: Introductionmentioning

confidence: 99%

Silodosin, an α<sub>1A</sub>-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow

Goi

Tomiyama²,

Maruyama³

et al. 2016

Pharmacology

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Background/Aims: This study was performed to investigate the detailed mechanism underlying the effects of the selective α_1A-adrenoceptor antagonist, silodosin, on bladder function in a rat model of atherosclerosis-induced chronic bladder ischemia (CBI). Methods: The CBI model was prepared by balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, the CBI rats received either silodosin or vehicle alone subcutaneously for 8 weeks. Rats received a 2% cholesterol diet throughout the experiment. Bladder blood flow (BBF) was measured. Immunohistochemical staining was performed to determine the nerve distribution and nerve growth factor expression in the bladder. Bladders were used for muscle strip contraction analysis. The expression levels of muscarinic M2 and M3 receptors were measured. Results: Silodosin abrogated the decrease in BBF in CBI rats. Silodosin prevented the decrease in nerve distribution and increase in nerve growth factor expression in the CBI model. Bladder contractile response was reduced in the CBI group. Silodosin ameliorated the effect on the bladder contractile response. The level of muscarinic M3 receptor mRNA present in the bladder of CBI rats was increased by silodosin. Conclusion: The results of this study suggest that silodosin ameliorates the denervation of the bladder and effects on detrusor contractile function under ischemic conditions by restoring BBF.

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Alteration of urothelial‐mediated tone in the ischemic bladder: Role of eicosanoids

Abstract: Our studies suggest loss of urothelial-mediated tone and LTs-mediated smooth muscle instability in the chronically ischemic/hypoxic bladder.

Cited by 41 publications

References 23 publications

Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil

Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil

Lower Urinary Tract Symptoms and Aging: The Impact of Chronic Bladder Ischemia on Overactive Bladder Syndrome

Silodosin, an α<sub>1A</sub>-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow

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