Effect of phosphodiesterase type 4 inhibitor rolipram on cyclophosphamide-induced cystitis in rats

Buyuknacar, Hacer Sinem; Kumcu, Eda Karabal; Göçmen, Cemil; Önder, Serpil

doi:10.1016/j.ejphar.2008.02.022

Cited by 17 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under pathological conditions such as inflammation, the key parameters of the micturition cycle and voiding could be assessed at the most critical time periods without any forced bladder infusion but rather upon endogenous stimulation of diuresis. Commonly used models of cystomanometry are based on the infusion of the bladder with a determined flow rate of saline . The model presented herein is based on a different approach with a bladder filling by increased diuresis triggering micturitions by a more physiological way.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions

Monjotin

Farrié

Vergnolle

et al. 2016

Neurourology and Urodynamics

View full text Add to dashboard Cite

Aims: To establish a new approach to cystometry using telemetry in conscious rats and to use this technique to determine the role of conscious decision making processes with respect to the initiation of voiding in physiological, inflammatory, and painful conditions. Methods: The pressure transducer of a telemetric transmitter was implanted in the dome of the urinary bladder. After a recovery period of at least 1 month, several investigations of urodynamic parameters were performed after diuresis activation by a pulse of furosemide. The model was characterized by tolterodine and mirabegron under physiological conditions and same animals were reused to evaluate the modification of the voiding pattern under bladder inflammation induced by cyclophosphamide. Results: The quality of traces and measurement of parameters recorded telemetrically were comparable to those with conventional cystometry. Furosemide induced a reproducible transient increase of urine production and a series of voids that persisted for 60 min. Tolterodine reduced the amplitude of micturition contractions although mirabegron was devoid of any effect. Seven hours after injection of CYP, voiding frequency increased significantly and the micturition amplitude contraction was not altered. However, the mean volume voided during individual micturitions and the total voided volume decreased. During a second exposure to furosemide 24H after CYP injection, the micturition pattern returned to control, however, the micturition volume was still lower than in control. Conclusion: This telemetric model appears to be as accurate as previously described in conscious conventional cystometry, and allows the repeated evaluation of compounds which may modulate the voiding patterns. Neurourol.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Commonly used models of cystomanometry are based on the infusion of the bladder with a determined flow rate of saline. 8,14 The model presented herein is based on a different approach with a bladder filling by increased diuresis triggering micturitions by a more physiological way.…”

Section: Discussionmentioning

confidence: 99%

Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions

Monjotin

Farrié

Vergnolle

et al. 2016

Neurourology and Urodynamics

View full text Add to dashboard Cite

show abstract

“…cAMP, via PKA activation, regulates smooth muscle function by targeting the activity of various K + and Ca 2+ channels, thus reducing the myocyte excitability and contractility [13,15,16]. The cAMP and cGMP pathways have a major role in detrusor and urethra, respectively, relaxation, and thus PDE4 and PDE5 inhibitors have been proposed for the treatment of overactive bladder and lower urinary tract symptoms (LUTS), respectively [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck

Ribeiro¹,

Fernandes²,

Martínez‐Sáenz

et al. 2014

The Journal of Sexual Medicine

View full text Add to dashboard Cite

Introduction Phosphodiesterase type 5 (PDE5) inhibitors act as effective drugs for the treatment of lower urinary tract symptom (LUTS). There is a poor information, however, about the role of the PDE4 inhibitors on the bladder outflow region contractility. Aim To investigate PDE4 expression and the relaxation induced by the PDE4 inhibitor rolipram versus that induced by the PDE5 blockers sildenafil and vardenafil, in the pig and human bladder neck. Methods Immunohistochemistry for PDE4 expression, myographs for isometric force recordings and fura-2 fluorescence for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension for rolipram in bladder neck samples were used. Main Outcome Measures PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension. Results PDE4 expression was observed widely distributed in the smooth muscle layer of the pig and human bladder neck. On urothelium-denuded phenylephrine (PhE)-precontracted strips of pig and human, rolipram, sildenafil and vardenafil produced concentration-dependent relaxations with the following order of potency: rolipram> > sildenafil>vardenafil. In pig, the adenylyl cyclase activator forskolin potentiated rolipram-elicited relaxation, whereas protein kinase A (PKA) blockade reduced such effect. On potassium-enriched physiological saline solution (KPSS)-precontracted strips, rolipram evoked a lower relaxation than that obtained on PhE-stimulated preparations. Inhibition of large (BKCa) and intermediate (IKCa) conductance Ca2+-activated K+ channels, neuronal voltage-gated Ca2+ channels, nitric oxide (NO) and hydrogen sulfide (H2S) synthases reduced rolipram responses. Rolipram inhibited the contractions induced by PhE without reducing the PhE-evoked [Ca2+]i increase. Conclusions PDE4 is present in the pig and human bladder neck smooth muscle, where rolipram exerts a much more potent relaxation than that elicited by PDE5 inhibitors. In pig, rolipram-induced response is produced through the PKA pathway involving BKCa and IKCa channel activation and [Ca2+]idesensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release.

show abstract

“…The bladder is not filled artificially with saline but urine following as part of an endogenous diuresis. Consequently, bladder filling and emptying operate in a more physiological condition (Buyuknacar et al , ; Andersson et al , ). As a result, the timing of a void is determined by the animal, a conscious decision, and not only by activation of reflexes when the bladder is full.…”

Section: Discussionmentioning

confidence: 99%

F16357, a novel protease‐activated receptor 1 antagonist, improves urodynamic parameters in a rat model of interstitial cystitis

Monjotin

Gillespie

Farrié

et al. 2016

British J Pharmacology

View full text Add to dashboard Cite

Background and PurposeThe aims of the present study were to characterize the role of PAR1 in rat bladder under inflammatory conditions and determine whether a selective PAR1 antagonist, F16357, can prevent the pathophysiological symptoms of cyclophosphamide‐induced interstitial cystitis (IC).Experimental ApproachImmunohistochemistry, contractile activity in isolated bladder and urodynamics were determined before and after cyclophosphamide treatment. F16357 was administered intravesically during the acute phase of inflammation, and effects on PAR1 and PAR1‐related bladder contraction evaluated 24 h after cyclophosphamide injection. Urodynamics and associated voided volumes were recorded 7 and 24 h after cyclophosphamide.Key ResultsIn control conditions, PAR1 was present only in some umbrella cells. Cyclophosphamide disrupted the urothelium and expression of PAR1 by all remaining urothelial cells. After F16357 treatment, urothelial damage was absent and PAR1 immunoreactivity similar to control tissues. Thrombin and TFLLR‐NH2 induced bladder contractions. These were increased in inflammatory conditions and antagonized by F16357 in a concentration‐dependent manner. In telemetric experiments, furosemide increased urine production and voiding frequency for 60 min, 7 h after cyclophosphamide injection. Intravesical administration of F16357 blocked these changes with a return to a physiological profile; 24 h after cyclophosphamide, the volume of micturition was still lower with no increase in number of micturitions. F16357 30 μM reduced the number of micturitions and improved bladder capacity, but did not affect diuresis. Under similar experimental conditions, lidocaine 2% induced comparable effects.Conclusions and ImplicationsPAR1 is expressed in rat bladder, overactivated in inflammatory conditions and involved in bladder function and sensation. F16357 could represent an interesting candidate for IC treatment.

show abstract

Effect of phosphodiesterase type 4 inhibitor rolipram on cyclophosphamide-induced cystitis in rats

Cited by 17 publications

References 27 publications

Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions

Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions

Powerful Relaxation of Phosphodiesterase Type 4 Inhibitor Rolipram in the Pig and Human Bladder Neck

F16357, a novel protease‐activated receptor 1 antagonist, improves urodynamic parameters in a rat model of interstitial cystitis

Contact Info

Product

Resources

About