Ameliorating effects of cloperastine on dysfunction of the urinary bladder caused by cerebral infarction in conscious rats

2009 ◽  
Vol 87 (11) ◽  
pp. 893-899 ◽  
Author(s):  
Gen Yamamoto ◽  
Fumio Soeda ◽  
Tetsuya Shirasaki ◽  
Kazuo Takahama
Keyword(s):  
Urinary Bladder ◽  
Cerebral Infarction ◽  
Flow Rate ◽  
Bladder Capacity ◽  
Left Middle Cerebral Artery ◽  
Sprague Dawley ◽  
Urinary Bladder Dysfunction ◽  
Sprague Dawley Rats ◽  
Urethral Resistance ◽  
Effective Doses

We investigated the effects of the centrally acting antitussives dextromethorphan and cloperastine on urinary bladder dysfunction 24 h after cerebral infarction in rats using the cystometry technique. First, cystometrography was performed in conscious male Sprague–Dawley rats. Cerebral infarction was then induced by occlusion of the left middle cerebral artery. Twenty-four hours after cerebral infarction, the effect of each drug on micturition disorder was estimated for 5 parameters: bladder capacity, maximum voiding pressure, micturition latency, flow rate, and urethral resistance. Cerebral infarction markedly reduced bladder capacity, micturition latency, and flow rate and increased urethral resistance. After cerebral infarction, intravenous dosing of saline had no effect on these parameters. Dextromethorphan (20 mg/kg) and cloperastine (2.5 and 5.0 mg/kg) at antitussive effective doses significantly increased bladder capacity and micturition latency. Unlike dextromethorphan, cloperastine ameliorated decreases in flow rate and increases in urethral resistance caused by cerebral infarction. These results suggest that cloperastine may have therapeutic value for the treatment of disorders of the micturition reflex associated with cerebral infarction, and that the drug may become a base compound from which to develop more active drugs for such disorders.

The role of the peripheral cannabinoid system in the pathogenesis of detrusor overactivity evoked by increased intravesical osmolarity in rats

2015 ◽  
Vol 93 (8) ◽  
pp. 721-726 ◽  
Author(s):  
Kajetan Juszczak ◽  
Piotr Maciukiewicz
Keyword(s):  
Urinary Bladder ◽  
Detrusor Overactivity ◽  
Cannabinoid Receptors ◽  
Bladder Capacity ◽  
Pressure Profile ◽  
Intravesical Instillation ◽  
Motility Index ◽  
Urinary Bladder Dysfunction ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

The cannabinoid receptors CB1 and CB2 are localized in the urinary bladder and play a role in the regulation of its function. We investigated the pathomechanisms through which hyperosmolarity induces detrusor overactivity (DO). We compared urinary bladder activity in response to blockade of CB1 and CB2 receptors using AM281 and AM630, respectively, in normal rats and after hyperosmolar stimulation. Experiments were performed on 44 rats. DO was induced by intravesical instillation of hyperosmolar saline. Surgical procedures and cystometry were performed under urethane anaesthesia. The measurements represent the average of 5 bladder micturition cycles. We analysed basal, threshold, and micturition voiding pressure; intercontraction interval; compliance; functional bladder capacity; motility index; and detrusor overactivity index. The blockage of CB1 and CB2 receptors diminished the severity of hyperosmolar-induced DO. In comparison with naïve animals the increased frequency of voiding with no significant effect on intravesical voiding pressure profile was observed as a result of the blockage of CB1 and CB2 receptors. These results demonstrate that hyperosmolar-induced DO is mediated by CB1 and CB2 receptors. Therefore, the cannabinoid pathway could potentially be a target for the treatment of urinary bladder dysfunction.

Abstract 20074: Hemodynamic Profile of Prolonged Normothermic, Mild Hypothermic, and Deep Hypothermic Emergency Cardiopulmonary Bypass Reperfusion in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ingrid A Magnet ◽  
Florian Ettl ◽  
Andreas Schober ◽  
Alexandra-Maria Warenits ◽  
Christoph Testori ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Flow Rate ◽  
Mild Hypothermia ◽  
Temperature Profiles ◽  
Sprague Dawley ◽  
Flow Rates ◽  
Circulating Water ◽  
Sprague Dawley Rats ◽  
Hemodynamic Profile ◽  
75Th Quartile

Background: The hemodynamic profile of rats randomized into prolonged normothermic (NT, 37±0.5°C), mild hypothermic (MH, 33±0.5°C) or deep hypothermic (DH, 27±0.5°C) reperfusion with emergency cardiopulmonary bypass (ECPB), following refractory ventricular fibrillation cardiac arrest (VF CA) was explored. Methods: Fifty adult male Sprague-Dawley rats were put on bypass for 15 min, following 10 min of VF CA. The ECPB setup included a circulating water bath which temperature controlled all animals at target. After 15 min, rats were defibrillated, weaned from bypass, and controlled at 33°C (MH, DH) or 37°C (NT) externally. All rats received a single dose of epinephrine (30 μg/kg), heparin and sodium bicarbonate with the crystalloid priming of the ECPB circuit. ECPB flow rate was kept at 100 mL/kg in all groups. Mean arterial pressure (MAP) was continuously monitored in the femoral artery and is presented as median with 25th/75th quartile mmHg. Results: See figure. There was no difference in MAP before or during CA. For the first 5 min of resuscitation, MAP at a given ECPB flow rate was highest in the DH group (DH 84(69;89), MH 51(49;61), NT 48(37;55) , p = <.001). This was reversed during the last 5 min on bypass (DH 35(30;42), MH 44(37;64), NT 42(33;67), p = .034). For 10 min off bypass, the DH group was relatively hypotensive (DH 46(40;62, MH 64(60;77), NT 61(54;77), p = .005), which was again reversed for the remaining post resuscitation period (DH 68(60;78), MH 59(54;66), NT 53(49;62), p = .008). Conclusions: While the temperature profiles of NT and MH reperfusion were similar, DH caused initially higher pressures followed by a period of hypotension as compared to NT and MH groups at identical epinephrine doses and ECPB flow rates. Off bypass, DH animals were again relatively hypotensive, coinciding with their rewarming to mild hypothermia. Further experiments are needed to determine the cause of this, like hypothermic vasoconstriction, or altered pharmacokinetics.

Mechanism underlying diuretic effect of l-NAME at a subpressor dose

2001 ◽  
Vol 281 (3) ◽  
pp. F414-F419 ◽  
Author(s):  
Mingyu Liang ◽  
Theresa J. Berndt ◽  
Franklyn G. Knox
Keyword(s):  
Proximal Tubule ◽  
Flow Rate ◽  
Nitrate Concentration ◽  
Distal Tubule ◽  
No Synthase ◽  
Urine Flow ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Renal Tubular ◽  
Nitrite Nitrate

The diuretic effects of nitric oxide (NO) synthase inhibitors administered at subpressor dose in rats are controversial, and the tubular segments involved are not known. In the present study, we examined the effect of N ω-nitro-l-arginine methyl ester (l-NAME) at a subpressor dose on renal interstitial NO and cGMP activity and on renal tubular segmental reabsorption of fluid in the rat. Intravenous infusion of l-NAME at 1 μg · kg−1 · min−1 in Sprague-Dawley rats ( N = 8), which did not alter mean arterial pressure or glomerular filtration rate, significantly increased urine flow rate (Uv; from 78.2 ± 12.7 to 117.1 ± 14.9 μl/min, P < 0.05). Paradoxically, this effect of l-NAME was concomitant with significant increases in nitrite/nitrate (from 10.79 ± 1.20 to 16.50 ± 2.60 μM, P < 0.05) and cGMP (from 0.65 ± 0.09 to 0.98 ± 0.18 nM, P < 0.05) concentrations in renal cortical microdialysate as well as the nitrite/nitrate concentration in the medullary microdialysate. Micropuncture studies in the superficial nephron revealed that l-NAME significantly increased the flow rate (from 8.3 ± 0.9 to 12.2 ± 1.2 nl/min, P < 0.05) and fractional delivery of fluid to the distal tubule, but not those in the late proximal tubule. In conclusion, l-NAME, at the subpressor dose used in this study, increased renal nitrate/nitrite and cGMP and inhibited fluid reabsorption in tubular segments between the late proximal tubule and the distal tubule of superficial nephrons.

Failure of tubule fluid osmolarity to affect feedback regulation of glomerular filtration

1980 ◽  
Vol 239 (5) ◽  
pp. F427-F432 ◽  
Author(s):  
J. P. Briggs ◽  
J. Schnermann ◽  
F. S. Wright
Keyword(s):  
Flow Rate ◽  
Feedback Regulation ◽  
Solute Concentration ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Perfusion Flow ◽  
Sprague Dawley Rats ◽  
Nacl Concentration ◽  
Osmotic Agents ◽  
Feedback Responses

Experiments were performed in Sprague-Dawley rats in order to distinguish between sodium chloride and total solute concentration as possible luminal signals capable of eliciting tubuloglomerular feedback responses. Early proximal flow rate (VEP), an index of nephron filtration rate, was measured without perfusion of the loop of Henle and during retrograde perfusion with solutions containing 20, 35, 60 to 100 mM NaCl and varying amounts of either urea or mannitol to achieve total solute concentrations of 130, 280, or 400 mosM. Perfusion flow rate was kept constant at 20 nl/min. Perfusion with a solution containing 20 mM NaCl and made hypo-, iso-, or hypertonic with urea or mannitol caused little or no change in VEP. Perfusion with a 35 mM NaCl solution made hypo-, iso-, or hypertonic with mannitol resulted in a fall of VEP of 6-7 nl/min. When NaCl concentration was 60 mM, VEP fell by 10-14 nl/min with solutions made hypo-, iso-, or hypertonic with urea or mannitol. With 100 mM NaCl solutions made hypo-, iso-, or hypertonic with mannitol, VEP fell approximately 12 nl/min. These results indicate that feedback responses are determined by the NaCl concentration of the perfusate and that this NaCl dependency is not modified by varying perfusate osmolarity between 130 and 400 mosM with urea or mannitol as osmotic agents.

scholarly journals Tubuloglomerular feedback in Dahl rats

1998 ◽  
Vol 274 (6) ◽  
pp. R1561-R1569 ◽  
Author(s):  
Finn M. Karlsen ◽  
Paul P. Leyssac ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Flow Rate ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Compensatory Response ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats ◽  
Intratubular Pressure ◽  
Low Salt ◽  
Experimental Rat Model

We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether this was due to a decreased activity of either the myogenic or the tubuloglomerular feedback (TGF) response, we tested the TGF response in both Dahl-S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated in the closed-loop mode with a videometric technique, in which the response in late proximal flow rate to perturbations in Henle flow rate was measured. All Dahl rats showed a similar compensatory response to perturbations around the natural operating point, with a TGF response that was more efficient than in normotensive Sprague-Dawley rats. No evidence of decreased TGF responsiveness in hypertensive Dahl-S rats was found. The results suggest that the loss of autoregulation in hypertensive Dahl-S rats is due to a compromised myogenic response. We also measured the free-flow proximal intratubular pressure in Dahl rats. Perfectly regular oscillations were demonstrated in all Dahl series, including the hypertensive Dahl-S rats. This is the first demonstration of regular oscillations in an experimental rat model of hypertension.

Oscillations of tubular pressure, flow, and distal chloride concentration in rats

1989 ◽  
Vol 256 (6) ◽  
pp. F1007-F1014 ◽  
Author(s):  
N. H. Holstein-Rathlou ◽  
D. J. Marsh
Keyword(s):  
Flow Rate ◽  
Fluid Velocity ◽  
Chloride Concentration ◽  
Feedback Mechanism ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Mean Values ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Chloride Activity

Previous experiments have shown oscillations in proximal tubular pressure in halothane-anesthetized rats. Such oscillations should be due to oscillations in flow rate and should cause periodic oscillations in both distal tubular chloride concentration and distal tubular pressure. The purpose of the study was to test these predictions. In halothane-anesthetized Sprague-Dawley rats, distal tubular chloride activity was measured with Cl- -sensitive electrodes, and late proximal flow rate was measured by pulse injection of boluses of solutions containing rhodamine dextran. Bolus velocity was detected by videomicroscopy. The time resolution was 2 s. All four variables oscillated with the same frequency, approximately 35 mHz. The amplitude of the flow and the chloride oscillations were 28 and 10%, respectively, of the mean values. Proximal fluid velocity led proximal pressure by 1.5 +/- 0.4 s, whereas distal chloride activity lagged proximal pressure by 8.9 +/- 0.8 s. The distal pressure lagged the proximal pressure by 1.05 +/- 0.38 s. It is concluded that there is a significant variation in distal chloride activity, the magnitude of which appears to be sufficient to account for the observed flow variations through the operation of the tubuloglomerular feedback mechanism.

scholarly journals Expression and function of transforming growth factor-β isoforms and cognate receptors in the rat urinary bladder following cyclophosphamide-induced cystitis

2013 ◽  
Vol 305 (9) ◽  
pp. F1265-F1276 ◽  
Author(s):  
Eric J. Gonzalez ◽  
Beatrice M. Girard ◽  
Margaret A. Vizzard
Keyword(s):  
Urinary Tract ◽  
Growth Factor ◽  
Urinary Bladder ◽  
Lower Urinary Tract ◽  
Transforming Growth Factor ◽  
Bladder Capacity ◽  
Transforming Growth Factor Β ◽  
Rat Urinary Bladder ◽  
Urinary Bladder Dysfunction ◽  
Lower Urinary

Numerous proinflammatory cytokines have been implicated in the reorganization of lower urinary tract function following cyclophosphamide (CYP)-induced cystitis. The present study investigated the functional profile of three pleiotropic transforming growth factor-β (TGF-β) isoforms and receptor (TβR) variants in the normal and inflamed (CYP-induced cystitis) rat urinary bladder. Our findings indicate that TGF-β (1, 2, and 3) and TβR (1, 2, and 3) transcript and protein expression were regulated to varying degrees in the urothelium or detrusor smooth muscle following intermediate (48 h; 150 mg/kg ip) or chronic (75 mg/kg ip; once every 3 days for 10 days), but not acute (4 h; 150 mg/kg ip), CYP-induced cystitis. Conscious, open-outlet cystometry was performed to determine whether aberrant TGF-β signaling contributes to urinary bladder dysfunction following intermediate (48 h) CYP-induced cystitis. TβR-1 inhibition with SB505124 (5 μM) significantly (p ≤ 0.001) decreased voiding frequency and increased bladder capacity (2.5-fold), void volume (2.6-fold), and intercontraction intervals (2.5-fold) in CYP-treated (48 h) rats. Taken together, these results provide evidence for 1) the involvement of TGF-β in lower urinary tract neuroplasticity following urinary bladder inflammation, 2) a functional role of TGF-β signaling in the afferent limb of the micturition reflex, and 3) urinary bladder TβR-1 as a viable target to reduce voiding frequency with cystitis.

scholarly journals Diabetes slows the recovery from urinary incontinence due to simulated childbirth in female rats

2007 ◽  
Vol 293 (2) ◽  
pp. R950-R955 ◽  
Author(s):  
Ja-Hong Kim ◽  
Xiao Huang ◽  
Guiming Liu ◽  
Courtenay Moore ◽  
James Bena ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
External Sphincter ◽  
Bladder Capacity ◽  
Diabetic Rats ◽  
Female Rats ◽  
Sprague Dawley ◽  
Leak Point Pressure ◽  
Sprague Dawley Rats ◽  
Point Pressure ◽  
Vaginal Distension

This study was done to test the hypothesis that simulated vaginal birth by vaginal distension (VD) causes more severe urinary incontinence and slower recovery in diabetic rats. After measuring baseline leak point pressure (LPP) in 16 diabetes mellitus (DM) and 16 age- and weight-matched control (Ct) female Sprague-Dawley rats, these animals underwent either VD or sham VD (sham). Four and ten days after the procedures, LPP and conscious cystometry were assessed. Tissues were then harvested and examined by light microscopy. LPP at baseline was equal among all four groups. Four days after VD, LPP in both VD groups dropped to significantly lower levels than in sham rats ( P < 0.001). Moreover, LPP in the DM+VD group was significantly lower than in the Ct+VD group. At 10 days, LPP in the Ct+VD group had recovered to its baseline value, whereas the LPP in the DM+VD group remained significantly reduced. DM rats had larger bladder capacity and longer voiding intervals than Ct rats. Histological findings included more severe damage to the external sphincter striated musculature of the urethra in DM+VD group compared with Ct+VD. In conclusion, these findings suggest that DM causes increased severity and delayed functional recovery from the effects of simulated childbirth.

scholarly journals Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

2014 ◽  
Vol 307 (7) ◽  
pp. R893-R900 ◽  
Author(s):  
Gerald C. Mingin ◽  
Abbey Peterson ◽  
Cuixia Shi Erickson ◽  
Mark T. Nelson ◽  
Margaret A. Vizzard
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Urinary Bladder ◽  
Protein Expression ◽  
Social Stress ◽  
Bladder Dysfunction ◽  
Bladder Capacity ◽  
Bladder Function ◽  
Nerve Growth ◽  
Urinary Bladder Dysfunction

Social stress may play a role in urinary bladder dysfunction in humans, but the underlying mechanisms are unknown. In the present study, we explored changes in bladder function caused by social stress using mouse models of stress and increasing stress. In the stress paradigm, individual submissive FVB mice were exposed to C57BL/6 aggressor mice directly/indirectly for 1 h/day for 2 or 4 wk. Increased stress was induced by continuous, direct/indirect exposure of FVB mice to aggressor mice for 2 wk. Stressed FVB mice exhibited nonvoiding bladder contractions and a decrease in both micturition interval (increased voiding frequency) and bladder capacity compared with control animals. ELISAs demonstrated a significant increase in histamine protein expression with no change in nerve growth factor protein expression in the urinary bladder compared with controls. Unlike stressed mice, mice exposed to an increased stress paradigm exhibited increased bladder capacities and intermicturition intervals (decreased voiding frequency). Both histamine and nerve growth factor protein expression were significantly increased with increased stress compared with control bladders. The change in bladder function from increased voiding frequency to decreased voiding frequency with increased stress intensity suggests that changes in social stress-induced urinary bladder dysfunction are context and duration dependent. In addition, changes in the bladder inflammatory milieu with social stress may be important contributors to changes in urinary bladder function.

Sign in / Sign up

Export Citation Format

Share Document