Do atherosclerosis and chronic bladder ischemia really play a role in detrusor dysfunction of old age?

doi:10.1016/j.urology.2004.08.055

Urology

Volume 65, Issue 1, January 2005, Pages 181-184

https://doi.org/10.1016/j.urology.2004.08.055 Get rights and content

Abstract

Objectives

To determine whether atherosclerosis-induced chronic pelvic ischemia plays a role in the pathogenesis of aging bladder dysfunction.

Methods

Old (70 weeks of age), apolipoprotein E gene knockout (APOEKO) mice, known to develop atherosclerosis spontaneously were used. A group of 70-week-old C57B mice were used as controls. The mice were killed and bladder smooth muscle strips obtained for in vitro contractile force determinations. The maximal contractions in response to 110 mM KCl, 10⁻⁵ M bethanechol, and resting muscle tone were compared. The abdominal aortas and iliac arteries were harvested from the mice, and computerized image analysis was used to determine the percentage of surface area of atherosclerosis in each mouse.

Results

Although the APOEKO mice had massive atherosclerosis of the abdominal aortas and iliac arteries (lesion surface area ± SEM 15.93% ± 3.02%, n = 4), the control mice (n = 5) had no atherosclerosis at all. No statistically significant difference was found in detrusor function (KCl 0.48 ± 0.11 versus 0.49 ± 0.05, bethanechol 0.11 ± 0.02 versus 0.13 ± 0.04, tone 0.063 ± 0.019 versus 0.07 ± 0.004, respectively) between the APOEKO mice (n = 6) and the control mice (n = 6).

Conclusions

Pelvic atherosclerosis caused no statistically significant changes in bladder smooth muscle contractile responses to bethanechol, KCl, or resting tone. The difference between these and previously reported results may have been a result of the more gradual onset of atherosclerosis in our model, which better mimics pelvic organ ischemia in the elderly.

Section snippets

Bladder tissue preparation

Male apolipoprotein E gene knockout (APOEKO) on C57Bl/6 background mice was used. These mice are known to develop massive atherosclerosis during their lives.³ Male C57Bl/6 mice were used as controls. Old mice (aged 70 ± 2 weeks) were killed by anesthetic overdose with Avertin (2,2,2-tribromoethanol/tert-amyl alcohol). Their bladders were immediately removed and washed several times in cold (4°C) physiologic salt solution (PSS; 140 mM NaCl; 4.7 mM KCl; 1.2 mM MgSO₄; 1.6 mM CaCl₂; 1.2 mM Na₂HPO₄;

Atherosclerosis

The 70-week-old APOEKO mice had extensive atherosclerosis of the abdominal aortas and iliac arteries (Fig. 1). The atherosclerotic lesion area was 15.93% ± 3.02% of the arterial inner surface area (n = 4). The control C57Bl/6 mice (n = 5) had no atherosclerosis at all (Fig. 2). The arteries of one C57Bl/6 and 2 APOEKO mice were not available for evaluation.

Detrusor function

Although the APOEKO mice demonstrated massive abdominal and pelvic atherosclerosis, no statistically significant difference was found in

Comment

Lower urinary tract dysfunction as mirrored by LUTS is very common in the elderly, with up to 30% of elderly people suffering from incontinence and a similar number complaining of obstructive symptoms.⁶ Elderly men are almost five times more likely to seek medical advice because of LUTS than are men aged 40 to 49 years.⁷ Although a very common cause of these symptoms is bladder outlet obstruction due to benign prostatic hyperplasia, this is by no means the only reason for these symptoms. It has

Conclusions

Gradually developing atherosclerosis and the presumed chronic bladder ischemia associated with it probably do not significantly change the detrusor’s contractile response to agonists such as bethanechol and KCl or the detrusor’s resting tone. It is still possible, however, that atherosclerosis may influence other bladder functions in the elderly, such as compliance, bladder capacity, and overactivity, as well as cause LUTS through other indirect mechanisms such as by affecting the prostate or

References (23)

K.M. Azadzoi et al.
Overactivity and structural changes in the chronically ischemic bladder
J Urol
(1999)
M.H. Hofker et al.
Transgenic mouse models to study the role of APOE in hyperlipidemia and atherosclerosis
Atherosclerosis
(1998)
C.G. Chute et al.
The prevalence of prostatisma population-based survey of urinary symptoms
J Urol
(1993)
I. Araki et al.
Lower urinary tract symptoms in men and women without underlying disease causing micturition disordera cross-sectional study assessing the natural history of bladder function
J Urol
(2003)
M.H. Blanker et al.
Normal values and determinants of circadian urine production in older mena population based study
J Urol
(2002)
J. Nordling
The aging bladder—a significant but underestimated role in the development of lower urinary tract symptoms
Exp Gerontol
(2002)
A. Elbadawi et al.
Structural basis of geriatric voiding dysfunction. VII. Prospective ultrastructural/urodynamic evaluation of its natural evolution
J Urol
(1997)
R.D. Brierly et al.
A prospective controlled quantitative study of ultra structural changes in the under active detrusor
J Urol
(2003)
A. Benetos et al.
Influence of age, risk factors, and cardiovascular and renal disease on arterial stiffnessclinical applications
Am J Hypertens
(2002)
H.S. Gill et al.
The effects of short-term in-vivo ischemia on the contractile function of the rabbit urinary bladder
J Urol
(1988)

K.M. Azadzoi et al.

Increased leukotriene and prostaglandin release and over activity in the chronically ischemic bladder

J Urol

(2003)

Cited by (43)

Risk factors for male lower urinary tract symptoms: The role of metabolic syndrome and androgenetic alopecia in a Latin American population
2013, Urology
Citation Excerpt :
However, inflammatory, vascular, and neural mechanisms that do not depend on BPH may be involved in this pathogenesis. Hypotheses for this association include bladder neuropathy resulting from diabetes, use of diuretics, coincidence of sleep apnea disorder causing nocturia, chronic neural and vascular impairment in the detrusor muscle, increased parasympathetic neuronal loss, and sympathetic overactivity.6,25 Although our study confirms an association of MetS with LUTS, our results diverge from those of the Boston Area Community Health Survey.3
To evaluate the association of male lower urinary tract symptoms (LUTS) with metabolic syndrome (MetS) and androgenetic alopecia in a Latin American population.
We enrolled 907 patients for prospective evaluation at a single institution. LUTS were evaluated with the International Prostate Symptom Score (IPSS). Subjects were evaluated with respect to hypertension, diabetes, dyslipidemia, previous cardiovascular events, body mass index (BMI), waist and hip circumference, and a laboratorial investigation including prostate-specific antigen (PSA), C-reactive protein (CRP), and gonadal steroids. Alopecia was classified according to the Norwood-Hamilton scale.
Mean patient age was 61.0 years; 57.5% of subjects had moderate/severe LUTS; MetS was present in 17.2% of subjects and 53.9% were classified as bald. Age, hypertension, diabetes, dyslipidemia, alopecia, previous cardiovascular event, and elevated waist-to-hip ratio (WHR) were associated with moderate/severe LUTS and with storage symptoms (P <.05). On multivariable analysis, age (odds ratio [OR] 2.30, 95% confidence interval [CI] 1.63-3.25), cardiovascular events (OR 1.73, 95% CI 1.07-2.78), and WHR (OR 1.65, 95% CI 1.13-2.40) were independent predictors for LUTS. For storage symptoms, age (OR 1.80, 95% CI 1.28-2.54), cardiovascular event (OR 2.07, 95% CI 1.27-3.39), WHR (OR 1.54, 95% CI 1.06-2.25), and MetS (OR 1.70, 95% CI 1.01-2.86) were independent risk factors. Age and cardiovascular event were the only independent predictors for voiding symptoms.
Components of the MetS were strongly associated with moderate and severe LUTS. WHR and cardiovascular events were independent predictors of voiding and storage symptoms, and MetS was an independent predictor of storage symptoms. Alopecia was not an independent predictor of LUTS.
Animal Models of Lower Urinary Tract Dysfunction
2013, Animal Models for the Study of Human Disease
The function of the lower urinary tract is to store urine and periodically expel its contents through a reciprocal control of the contractile properties of the urinary bladder and its outflow tract. The decision to switch from storage to voiding modes depends upon integrating, in the central nervous system, sensory information from the bladder and controlling lower urinary tract function from the sacral spinal cord. Pathological or congenital alterations to any stage of this process can induce a combination of symptoms that include urgency and frequency, leakage of urine or pain. Animal models can be generated to characterise different stages of this complex control process to understand the particular biological defects that can lead to these pathologies. This chapter will address a number of lower urinary tract pathologies and how animal models can help in understanding them.
Association of lower urinary tract symptoms and the metabolic syndrome: Results from the boston area community health survey
2013, Journal of Urology
In this study we investigated the relationship between lower urinary tract symptoms as defined by the American Urological Association symptom index and the metabolic syndrome, and determined the relationship between individual symptoms comprising the American Urological Association symptom index and the metabolic syndrome.
The Boston Area Community Health Survey used a 2-stage cluster design to recruit a random sample of 2,301 men 30 to 79 years old. Analyses were conducted on 1,899 men who provided blood samples. Urological symptoms comprising the American Urological Association symptom index were included in the analysis. The metabolic syndrome was defined using a modification of the Adult Treatment Panel III guidelines. The association between lower urinary tract symptoms and the metabolic syndrome was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models.
Increased odds of the metabolic syndrome were observed in men with mild to severe symptoms (American Urological Association symptom index 2 to 35) compared to those with an American Urological Association symptom index score of 0 or 1 (multivariate OR 1.68, 95% CI 1.21–2.35). A statistically significant association was observed between the metabolic syndrome and a voiding symptom score of 5 or greater (multivariate adjusted OR 1.73, 95% CI 1.06–2.80) but not for a storage symptom score of 4 or greater (multivariate adjusted OR 0.94, 95% CI 0.66–1.33). Increased odds of the metabolic syndrome were observed even with mild symptoms, primarily for incomplete emptying, intermittency and nocturia. These associations were observed primarily in younger men (younger than 60 years) and were null in older men (60 years old or older).
The observed association between urological symptoms and the metabolic syndrome provides further evidence of common underlying factors between lower urinary tract symptoms and chronic conditions outside the urinary tract.
Erectile dysfunction and benign prostatic hyperplasia: Two frequent pathologies of the aging male
2012, Progres en Urologie - FMC
L’hyperplasie bénigne de prostate (HBP) et la dysfonction érectile (DE) sont deux affections fréquemment rencontrées chez l’homme de plus de 50 ans.
Une revue systématique de la littérature a été pratiquée sur Pubmed entre 1998 et 2012 utilisant les mots clés erectile dysfonction, benign prostatic hyperplasia et/ou low urinary tract symptoms.
Dix-huit articles d’intérêts ont été sélectionnés, dont dix études cliniques, quatre articles de science fondamentale, trois articles de pharmacologie et un article de revue. Il s’agit d’études rétrospectives dont le niveau de preuve est principalement 2b. Un lien statistique indépendant est retrouvé dans la plupart des études cliniques, et des hypothèses physiopathologiques communes comme l’athérosclérose, l’hyperactivité autonome sont avancées par les études fondamentales.
Il existe un lien statistique indépendant entre HBP et DE. L’utilisation d’iPDE-5 présente un intérêt aux regards des mécanismes physiopathologiques communs mis en évidence.
Benign prostatic hyperplasia (BPH) end erectile dysfunction (ED) are frequently observed in the aging male.
A systematic review of the literature was performed on Pubmed including the keywords “erectile dysfonction”, “benign prostatic hyperplasia” and/or “low urinary tract symptoms”.
Eighteen manuscripts were selected, including 10 retrospective clinical studies, four of basic science, three of pharmacology and a review article. A significant relationship was found in most of the studies, and physiopathological hypothesis as atherosclerosis and autonomic hyperactivity were enlighten.
A statistical independent relationship exists between BPH and ED. The use of PDE-5i could be interesting regarding the common pathological process involved.
Metabolic syndrome and urinary disorders
2012, Progres en Urologie
Le but de cet article est de faire le point et de discuter les interrelations entre syndrome métabolique (SM) et troubles sphinctériens, tout particulièrement le syndrome clinique d’hyperactivité vésicale.
Une analyse Pubmed/Medline sans limite temporelle ni de langue a été effectuée sur les mots clés « syndrome métabolique » et « vessie » (ou « troubles urinaires » ou « incontinence »). Tous les articles (revue ou recherche) ont été retenus, soit 119 articles.
Le SM est défini par la présence d’au moins trois des cinq critères suivants : 1) tour de taille supérieur à 102 cm ; 2) pression artérielle systolique supérieure ou égale à 130 mmHg, ou pression diastolique de plus de 85 mmHg, ou hypertension artérielle traitée ; 3) taux de HDL cholestérol inférieur à 40 mg/dL ou hyperlipidémie traitée ; 4) diabète de type 2 ou utilisation d’antidiabétique oraux ; 5) taux de triglycérides de plus de 150 mg/dL. Il existe épidémiologiquement une corrélation forte entre le SM et l’hyperactivité vésicale. Les mécanismes physiopathologiques pour expliciter cette hyperactivité (plutôt qu’un syndrome dysurie-retention) sont nombreux mais au premier rang figure l’hyperglycémie dont le rôle délétère sur les neurones parasympathiques pelviens est bien connu. Un lien et/ou un chevauchement syndromique entre SM et altération du système nerveux autonome peut parfois être évoqué comme facteur physiopathologique et/ou étiopathogénique.
Les liens entre SM et troubles urinaires sont fréquents et des facteurs physiopathologiques communs, notamment végétatifs, peuvent être évoqués.
The goal of this article is to review and discuss the various and numerous links between metabolic syndrome (MetS) and bladder, specially overactive bladder syndrome.
Pubmed/Medline analysis, without date or language limits, was conducted using the following keywords: “metabolic syndrome” and “bladder (or “incontinence” or “overactive bladder”). All types of papers were analysed (117).
MetS is defined as the presence of three or more of the following five characteristics: 1) waist circumference greater than 102 cm; 2) systolic blood pressure 130 mmHg or greater or diastolic blood pressure 85 mmHg or greater, or antihypertensive medication use; 3) HDL cholesterol less than 40 mg/dL or lipid medication use; 4) self- reported type 2 diabetes or increased blood sugar or diabetes medication use; 5) triglycerides greater than 150 mg/dL. In regard of epidemiolgy, there is a strong correlation between MetS and overactive bladder. Pathophysiological mechanisms to explain the relationship of storage symptoms rather than voiding phase symptoms with MetS include the influence of sustained hyperglycemia on the viability of parasympathetic neurons in the pelvic ganglion. A link or overlaps between MetS and alteration of autonomic nervous system can be hypothezised.
Links between Mets and urinary disorders are frequent and common pathophysiological factors can be frequently observed, particularly autonomic nervous system alterations.
Are metabolic syndrome and its components associated with lower urinary tract symptoms? Results from a Chinese male population survey
2012, Urology
To investigate the association between severity of lower urinary tract symptoms (LUTS) and metabolic syndrome (MetS) and its components in a large male population in China.
Data were collected from 3103 men attending the Fangchenggang Area Male Healthy and Examination Survey (FAMHES) from September 2009 to December 2009. LUTS were assessed by the International Prostate Symptom Score (IPSS) and MetS were defined using a modification of the Adult Treatment Panel III guidelines. Blood samples were drawn to determine serum lipids and glucose levels. Comprehensive information on demographic characteristics and medication was also collected through questionnaires. The association between LUTS and MetS was presented as odds ratios and 95% confidence intervals estimated using a logistic regression model.
The presence of MetS was not associated with the severity of LUTS (multivariate OR = 0.97, 95% CI = 0.67-1.39), but its subcategories of moderate or severe storage symptoms were inversely related to MetS (multivariate OR = 0.64, 95% CI = 0.44-0.91). Aging was observed to be a major risk factor for LUTS, such that men 60 years or older experienced 2-fold the odds of moderate or severe LUTS (OR = 2.79, 95% CI = 1.82-4.29) when compared with men 40 years or less). Component of MetS, such as systolic blood pressure, has increased odds for moderate or severe postmicturition symptoms but with no statistically significant results in multivariate analysis (multivariate OR = 1.22, 95% CI = 0.93-1. 60).
Our data suggest that the MetS is not associated with LUTS. However, for subcategory symptoms, decreased odds of MetS was observed in moderate or severe voiding storage symptoms.

View all citing articles on Scopus

View full text

Basic scienceDo atherosclerosis and chronic bladder ischemia really play a role in detrusor dysfunction of old age?

Abstract

Objectives

Methods

Results

Conclusions

Section snippets

Bladder tissue preparation

Atherosclerosis

Detrusor function

Comment

Conclusions

J Urol

Atherosclerosis

J Urol

J Urol

J Urol

Exp Gerontol

J Urol

J Urol

Am J Hypertens

J Urol

J Urol

Basic science
Do atherosclerosis and chronic bladder ischemia really play a role in detrusor dysfunction of old age?