Clopidogrel inhibits acetylcholine-induced contractions of urinary bladder in rat

Aim: Clopidogrel as thrombocyte Adenosine Diphosphate (ADP) receptor antagonist is used especially in peripheric artery diseases by lengthening hemorrhage time, disrupting thrombocyte aggregation and decreasing blood viscosity. It shows its antagonist effects through glycoprotein (Gp) IIb/IIIa complex ADP by preventing its activation. Although the usage area and activity is in the vascular system, there are no adequate studies showing the activity of Clopidogrel on smooth muscle contraction-relaxation mechanism. This study was conducted to investigate the effects of Clopidogrel on bladder contraction-relaxation mechanism.Material and Methods: In the present study, the bladder tissues taken from Wistar-Albino (n=7) intact female rats were used. After the decapitation, the longitudinal bladder tissues that were received 1-mm-thick, 8-mm length, and 2-mm-width, were hung in the 5-ml isolated organ bath that had Krebs-Ringer bicarbonate solution by applying 1.5 gr strain. After the bladder contractions were induced with 10 μM dose Acetylcholine (Ach), Clopidogrel was applied as two doses 0.1μM and 10μM in a noncumulative manner. The peak-to-peak (p-p) values and the values below the curve before and after the Clopidogrel application in the contraction induced with Ach were normalized as % change. The statistical analyses of the data were made in the SPSS 22.0 program by applying Paired T-Test. The p

PDF

___

1. Coyne KS, Sexton CC, Thompson, CL, et al. The prevalence of lower urinary tract symptoms (LUTS) in the U. S. A., the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. BJU Int 2009;104:352-60.
2. Ford AP, Cockayne DA. ATP and P2X purinoceptors in urinary tract disorders. Handb Exp Pharmacol 2011;202:485-526.
3. Liu G, Daneshgari F. Alterations in neurogenically mediated contractile responses of urinary bladder in rats with diabetes. Am J Physiol Renal Physiol 2005;288:1220-6.
4. Burnstock G. Introductory overview of purinergic signalling. Front Biosci 2011;3:896-900.
5. Aronsson P, Andersson M, Ericsson T, et al. Assessment and characterization of purinergic contractions and relaxations in the rat urinary bladder. Basic Clin. Pharmacol Toxicol 2010;107:603-13.
6. McMurray G, Dass N, Brading AF. Purinoceptor subtypes mediating contraction and relaxation of marmoset urinary bladder smooth muscle. Br J Pharmacol 1998;123:1579-86.
7. Suzuki H, Kokubun S. Subtypes of purinoceptors in rat and dog urinary bladder smooth muscles. Br J Pharmacol 1994;112:117-22.
8. Schror K. Antiplatelet drugs: a comparative review. Drugs 1995;50:7-28.
9. Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003;107:32-7.
10. Dorsam RT, Kunapuli SP. Central role of the P2Y12 receptor in platelet activation. J Clin Invest 2004;113: 340-5.
11. Herbert JM, Tissiner A, Defreyn G, et al. Inhibitory effect of clopidogrel on platelet adhesion and intimal profileration after arterial injury in rabbits. Arterioscler Thromb 1993;13:1171-9.
12. Chen Z, Jiang L, Chen Y, et al. COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Addition of clopidogrel to aspirin in 45852 patients with acute myocardial infarction: randomised placebo controlled trial. Lancet 2005;366:1607-21.
13. Yusuf S, Bijsterveld N, Moons A. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation: the Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. N Engl J Med 2001;345:494-502.
14. Kunapuli SP, Dorsam RT, Kim S, et al. Platelet purinergic receptors. Curr. Opin. Pharmacol 2003;3:175-80.
15. Beavers CJ, Naqvi IA. Clopidogrel.SourceStatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2018.
16. Pultar J, Wadowski PP, Panzer S, et al. Oral antiplatelet agents in cardiovascular disease. Vasa 2018;6:1-12.
17. Guglielmina F, Bertin R, Dorigo P, et al. Endothelium-independent vasorelaxation by ticlopidine and clopidogrel in rat caudal artery. J Phar Pharmacol 2011;63:1056-60.
18. Yu W, Sun X, Robson SC, et al. ADP-induced bladder contractility is mediated by P2Y12 receptor and temporally regulated by ectonucleotidases and adenosine signaling. FASEB J 2014;28:5288-98.
19. Haylen BT, Freeman RM, Swift SE, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint terminology and classification of the complications related directly to the insertion of prostheses (meshes, implants, tapes) and grafts in female pelvic floor surgery. Neurourol Urodyn 2011;30:2-12.
20. Irwin DE, Milsom I, Hunskaar S, et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: Results of the EPIC study. Eur Urol 2006;50:1306-14.
21. Malmsten UG, Molander U, Peeker R, et al. Urinary incontinence, overactive bladder, and other lower urinary tract symptoms: A longitudinal population-based survey in men aged 45-103 years. Eur Urol 2010;58:149-56.
22. Milsom I, Kaplan SA, Coyne KS, et al. Effect of bothersome overactive bladder symptoms on health-related quality of life, anxiety, depression, and treatment seeking in the United States: Results from EpiLUTS. Urology 2012;80:90-6.
23. McGrother CW, Donaldson MM, Hayward T, et al. Urinary storage symptoms and comorbidities: A prospective population cohort study in middle-aged and older women. Age Ageing 2006;35:16-24.
24. Apostolidis A, Averbeck MA, Sahai A, et al. Can we create a valid treatment algorithm for patients with drug resistant overactive bladder (OAB) syndrome or detrusor overactivity (DO)? Results from a think tank (ICI-RS 2015). Neurourol Urodyn 2017;36:882-93.