Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC268

Poster Communications

In vitro effects of ivabradin hydrochloride on carbachol-induced contractions of rat detrussor muscle

H. R. Aydin1, H. Turgut2, A. KURT3, R. Sahan3, A. AYAR3

1. Department of Urology, Recep Tayyip Erdogan University, Faculty of Medicine, Rize, Turkey. 2. Department of Urology, Akcaabat Hackali Baba Hospital, Trabzon, Turkey. 3. Department of Physiology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey.

Although pacemaker cells, resembling the interstitial Cajal cells of gastrointestinal tract, have been morphologically identified in the bladder it is not clear whether these cells play any significant role in bladder contractility abnormalities. If "funny (If)" pacemaker currents are involved in the generation of the spontaneous contractility of urinary bladder, the selective If current inhibitor ivabradin would be useful in the management of overactive bladder, characterised by uncontrolled contractions causing a set of symptoms including uncontrollable urgency, a condition still needs to be effectively treated. An editorial comment (Stamatiou et al 2008) have addressed this issue but no further clinical trial or experimental study being performed yet. Hence, the aim of this in vitro study was to investigate the effects of ivabradin on charbachol-induced isometric contractions of rat bladder smooth muscle. Urinary bladder strips were isolated from adult male Wistar rats and suspended in 20 ml water-jacketed tissue bath containing Krebs' solution at 37 0C and pH 7.4, constantly bubled with 95% O2-5% C02. Isometric contractions were recorded by using isometric force displacement transducers which were attached to a Biopac data acquisition system. After equilibration under resting tension of 0.5 g for 60-minute, bladder strips were contracted by bath applications of carbachol (CCh, 1 uM). Ivabradin (10 and 60 uM) was added to tissue bath either prior or after application of the agonist and resulting contractile activity was compared with the preceding contractile activity. Amplitude and area under force-time curves (AUC) of isometric contractions were evaluated. Ivabradin dose dependently inhibited both the peak amplitude and AUC values of the CCh-induced contractions in a concentration dependent manner. On the average, normalized AUC values of CCh-induced contractions was reduced to 47 ± 5.5 % (P<0.05) and 35 % ± 6 % (P<0.05) after application of 10 and 60 uM ivabradin (n=7 for each), respectively. In addition, pretreatment with ivabradin significantly attenuated the contractile responses to the CCh without significantly effecting the resting tension (30 uM ivabradin pre-treatment: 590± 120 mg (n=6) vs. without ivabradin pretreatment: 2565±461 mg, n=8, p<0.05). In conclusion, results of this in vitro study demonstrated that ivabradin inhihibits carbachol-induced contractions of rat bladder smooth muscle implicating that this agent may have potential to be used in the treatment of overactive bladder. Where applicable, experiments conform with Society ethical requirements

Where applicable, experiments conform with Society ethical requirements