Alterations in neurogenically mediated contractile responses of urinary bladder in rats with diabetes

2005 ◽  
Vol 288 (6) ◽  
pp. F1220-F1226 ◽  
Author(s):  
Guiming Liu ◽  
Firouz Daneshgari
Keyword(s):  
Urinary Bladder ◽  
Unknown Origin ◽  
Electrical Field Stimulation ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Detrusor Muscle ◽  
Sprague Dawley ◽  
Contractile Responses ◽  
Bladder Detrusor ◽  
Induced Changes

Diabetic bladder dysfunction (DBD) is among the most common and bothersome complications of diabetes mellitus. Autonomic neuropathy has been counted as the cause of DBD. In the present study, we compared the alterations in the neurogenically mediated contractile responses of urinary bladder in rats with streptozocin-induced diabetes, 5% sucrose-induced diuresis, and age-matched controls. Male Sprague-Dawley rats were divided into three groups: 9-wk diabetic rats, diuretic rats, and age-matched controls. Micturition and morphometric characteristics were evaluated using metabolic cage and gross examination of the bladder. Bladder detrusor muscle strips were exposed to either periodic electrical field stimulation (EFS) or to EFS in the presence of atropine, α,β-methylene adrenasine 5′-triphosphate, or tetrodotoxin. The proportions of cholinergic, purinergic, and residual nonadrenergic-noncholinergic (NANC) components of contractile response were compared among the three groups of animals. Diabetes caused a significant reduction of body weight compared with diuresis and controls, although the bladders of diabetic and diuretic rats weighed more than the controls. Both diabetes and diuresis caused significant increase in fluid intake, urine output, and bladder size. Diabetes and diuresis caused similarly increased response to EFS and reduced response to cholinergic component compared with controls. However, the purinergic response was significantly smaller in diuretic bladder strips compared with controls but not in diabetic rats. A residual NANC of unknown origin increased significantly but differently in diabetics and diuretics compared with controls. In conclusion, neurogenically mediated bladder contraction is altered in the diabetic rat. Diabetic-related changes do not parallel diuretic-induced changes, indicating that the pathogenesis of DBD needs further exploration.

β-NAD is a novel nucleotide released on stimulation of nerve terminals in human urinary bladder detrusor muscle

2006 ◽  
Vol 290 (2) ◽  
pp. F486-F495 ◽  
Author(s):  
Leanne T. Breen ◽  
Lisa M. Smyth ◽  
Ilia A. Yamboliev ◽  
Violeta N. Mutafova-Yambolieva
Keyword(s):  
Urinary Bladder ◽  
Neural Control ◽  
Electrical Field Stimulation ◽  
Specific Substrate ◽  
Detrusor Muscle ◽  
Hplc Fraction ◽  
Human Urinary Bladder ◽  
Adp Ribosyl Cyclase ◽  
Bladder Detrusor ◽  
Spontaneous Contractions

Endogenous nucleotides with extracellular functions may be involved in the complex neural control of human urinary bladder (HUB). Using HPLC techniques with fluorescence detection, we observed that in addition to ATP and its metabolites ADP, AMP and adenosine, electrical field stimulation (EFS; 4–16 Hz, 0.1 ms, 15 V, 60 s) of HUB detrusor smooth muscle coreleases novel nucleotide factors, which produce etheno-1 N6-ADP-ribose (eADPR) on etheno-derivatization at high temperature. A detailed HPLC fraction analysis determined that nicotinamide adenine dinucleotide (β-NAD+; 7.0 ± 0.7 fmol/mg tissue) is the primary nucleotide that contributes to the formation of eADPR. The tissue superfusates collected during EFS also contained the β-NAD+ metabolite ADPR (0.35 ± 0.2 fmol/mg tissue) but not cyclic ADPR (cADPR). HUB failed to degrade nicotinamide guanine dinucleotide (NGD+), a specific substrate of ADP ribosyl cyclase, suggesting that the activity of this enzyme in the HUB is negligible. The EFS-evoked release of β-NAD+ was frequency dependent and is reduced in the presence of tetrodotoxin (TTX; 0.3 μmol/l), ω-conotoxin GVIA (50 nmol/l), and botulinum neurotoxin A (BoNT/A; 100 nmol/l), but remained unchanged in the presence of guanethidine (3 μmol/l), ω-agatoxin IVA (50 nmol/l), or charbachol (1 μmol/l). Capsaicin (10 μmol/l) increased both the resting and EFS-evoked overflow of β-NAD+. Exogenous β-NAD+ (1 μmol/l) reduced both the frequency and amplitude of spontaneous contractions. In conclusion, we detected nerve-evoked overflow of β-NAD+ and ADPR in HUB. The β-NAD+/ADPR system may constitute a novel inhibitory extracellular nucleotide mechanism of neural control of the human bladder.

Pharmacologic responses of the mouse urinary bladder

Open Medicine ◽  
2009 ◽  
Vol 4 (2) ◽  
pp. 192-197 ◽  
Author(s):  
A. Canda ◽  
Christopher Chapple ◽  
Russ Chess-Williams
Keyword(s):  
Nitric Oxide ◽  
Urinary Bladder ◽  
Electrical Field Stimulation ◽  
Inhibitory Effect ◽  
Minor Role ◽  
Detrusor Muscle ◽  
Field Stimulation ◽  
Muscarinic Agonists ◽  
Electrical Field ◽  
M3 Receptor

AbstractThe aim of the study was to determine pathways involved in contraction and relaxation of the mouse urinary bladder. Mouse bladder strips were set up in gassed Krebs-bicarbonate solution and responses to various drugs and electrical field stimulation were obtained. Isoprenaline (b-receptor agonist) caused a 63% inhibition of carbachol precontracted detrusor (EC50=2nM). Carbachol caused contraction (EC50=0.3µM), responses were antagonised more potently by 4-DAMP (M3-antagonist) than methoctramine (M2-antagonist). Electrical field stimulation caused contraction, which was inhibited by atropine (60%) and less by guanethidine and α,β-methylene-ATP. The neurogenic responses were not potentiated by inhibition of nitric oxide synthase. Presence of an intact urothelium significantly depressed responses to carbachol (p=0.02) and addition of indomethacin and L-NNA to remove prostaglandin and nitric oxide production respectively did not prevent the inhibitory effect of the urothelium. In conclusion, b-receptor agonists cause relaxation and muscarinic agonists cause contraction via the M3-receptor. Acetylcholine is the main neurotransmitter causing contraction while nitric oxide has a minor role. The mouse and human urothelium are similar in releasing a factor that inhibits contraction of the detrusor muscle which is unidentified but is not nitric oxide or a prostaglandin. Therefore, the mouse may be used as a model to study the lower urinary tract.

Peritoneal Accumulation of Advanced Glycosylation End-Products in Diabetic Rats on Dialysis with Icodextrin

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 39-47 ◽  
Author(s):  
Jeong Ho Lee ◽  
Dheerendra K. Reddy ◽  
Rajiv Saran ◽  
Harold L. Moore ◽  
Zbylut J. Twardowski ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Glucose Solution ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Peritoneal Membrane ◽  
Sprague Dawley ◽  
Advanced Glycosylation End Products ◽  
Group I ◽  
End Products ◽  
Advanced Glycosylation

Objective To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and formation of advanced glycosylation end-products (AGEs) in the peritoneal membrane in the diabetic rat model of peritoneal dialysis (PD). Study Design Thirty-three male Sprague–Dawley rats weighing between 275 – 300 g were divided into 5 groups: group C ( n = 6), control rats with catheter but not dialyzed; group D ( n = 5), diabetic rats with catheter but not dialyzed; group G ( n = 7), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for the overnight exchange; group H ( n = 8), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I ( n = 7), diabetic rats dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges were performed three times daily with an instillation volume of 25 mL per exchange for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics. Results The level of immunostaining was lowest in group C and highest in group G. Significant differences were seen between group C and groups G, H, and I ( p < 0.001, p = 0.001, and p < 0.05 respectively). Significant differences were also found between group G and groups D and I ( p < 0.05 and p < 0.05 respectively). Over time, glucose concentration at the end of an exchange versus concentration at instillation (D/D0 glucose) decreased and dialysate-to-plasma ratio (D/P) of urea increased. Significant differences were found between groups C and H for D/D0 glucose (0.40 ± 0.01 vs 0.35 ± 0.01, p < 0.05); and between groups C and H for D/P urea (0.87 ± 0.03 vs 0.97 ± 0.02, p < 0.05). Conclusions These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solutions. We conclude that the use of icodextrin may be helpful in slowing the deterioration of the peritoneal membrane, prolonging its use for dialysis.

Contractile responses in intact and mucosa-denuded human ureter—a comparison with urinary bladder detrusor preparations

2018 ◽  
Vol 391 (8) ◽  
pp. 773-782 ◽  
Author(s):  
Melanie Roedel ◽  
Ursula Ravens ◽  
Michael Kasper ◽  
Manfred P. Wirth ◽  
Thomas A. Jepps ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Contractile Responses ◽  
Bladder Detrusor ◽  
Human Ureter

Mirabegron, A Selective β3-Adrenoceptor Agonist Causes an Improvement in Erectile Dysfunction in Diabetic Rats

2019 ◽  
Author(s):  
Didem Yilmaz-Oral ◽  
Ecem Kaya-Sezginer ◽  
Dilan Askin ◽  
Yesim Hamurtekin ◽  
Serap Gur
Keyword(s):  
Erectile Dysfunction ◽  
Pde5 Inhibitor ◽  
Corpus Cavernosum ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Sprague Dawley ◽  
Intracavernosal Injection ◽  
Relaxation Responses

Abstract Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.

C159 EFFECTS OF MELATONIN AND GHRELIN ON NEUROPEPTIDE-INDUCED CONTRACTILE RESPONSES OF URINARY BLADDER FROM DIABETIC RATS

2012 ◽  
Vol 11 (4) ◽  
pp. 120
Author(s):  
A. Tolekova ◽  
P. Hadzhibozheva ◽  
G. Ilieva ◽  
T. Georgiev ◽  
M. Kamburova
Keyword(s):  
Urinary Bladder ◽  
Diabetic Rats ◽  
Contractile Responses

Vascular responses to agonists in rat mesenteric artery from diabetic rats

1987 ◽  
Vol 65 (7) ◽  
pp. 1484-1490 ◽  
Author(s):  
Devendra K. Agrawal ◽  
John H. McNeill
Keyword(s):  
Diabetic Rats ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Diabetic Rat ◽  
Prostaglandin E ◽  
Contractile Responses ◽  
Alpha Adrenoceptor ◽  
Diabetic Model ◽  
Rat Mesenteric Artery ◽  
Adrenoceptor Agonists

The effect of diabetes on vascular smooth muscle function was investigated in the muscular arteries from spontaneously and chemically induced diabetic rats. Isolated ring segments of superior mesenteric arteries from BB diabetic and streptozotocin (STZ)-diabetic rats (12 weeks after onset of diabetes) were used for isometric tension studies. Contractile responses to alpha-adrenoceptor agonists (norepinephrine, methoxamine, phenylephrine, B-HT 920, guanabenz, SKF 89748-A), serotonin, and K+ were significantly higher in STZ-diabetic rat arteries as compared with the controls. In spontaneously diabetic rat arteries only the contractile responses to the putatively selective alpha2-adrenoceptor agonists, K+ and prostaglandin E1, were significantly increased. pD2 values of the agonists in both groups of diabetic arteries were not significantly different from the respective controls. Nifedipine inhibited all contractile responses in a dose-dependent fashion. The responses to K+ and alpha2-adrenoceptor agonists were attenuated to a greater extent by nifedipine in both groups of diabetic blood vessels. The calcium channel activator, BAY K 8644, produced a twofold increase in force of contraction in streptozotocin-diabetic and spontaneously diabetic rat arteries as compared with the responses in their respective controls. These results suggest caution in extrapolating all the findings from the streptozotocin-induced diabetic model to the spontaneously diabetic model. However, increased activity of calcium channels in vascular muscle cells in both groups of diabetics may be responsible, at least in part, for the increased vascular contractility in diabetes mellitus.

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