Does hypercholesterolemia affect the relaxation of the detrusor smooth muscle in rats? In vitro and in vivo studies


Bayrak S. , BALKANCI Z. D. , PEHLİVANOĞLU B. , KARABULUT İ. , KARAİSMAİLOĞLU S. , ERDEM A.

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, vol.388, no.7, pp.761-771, 2015 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 388 Issue: 7
  • Publication Date: 2015
  • Doi Number: 10.1007/s00210-014-1060-7
  • Title of Journal : NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
  • Page Numbers: pp.761-771

Abstract

To evaluate the effects of hypercholesterolemia on the relaxation function of the urinary bladder, we examined the physiological mechanisms involved in the isoproterenol-induced relaxation in isolated detrusor strips in vitro and voiding behavior in vivo in rats. Adult male Sprague-Dawley rats were fed standard (control, N = 16) or 4 % cholesterol diet (hypercholesterolemia, N = 17) for 4 weeks. Concentration-response curves for isoproterenol-induced relaxations in carbachol-precontracted detrusor muscle strips were recorded. The contributions of beta(2)- and beta(3)-adrenoceptors and ATP-dependent and Ca2+-dependent potassium channels to the relaxation response were investigated by using selective adrenergic agonists salbutamol and BRL 37344 and specific potassium channel inhibitors glibenclamide and charybdotoxin, respectively. Cystometrography was performed to assess bladder function. Hypercholesterolemic rats had higher serum cholesterol and low- and high-density lipoprotein levels than the controls with no sign of atherosclerosis. Isoproterenol-induced relaxation was significantly enhanced in the hypercholesterolemia group. Preincubation with the M-2 receptor antagonist attenuated the relaxation response in both groups. The relaxation responses to isoproterenol and salbutamol were similar in both groups, while BRL 37344 appeared to produce a greater relaxant effect in the hypercholesterolemic rats. Also, the inhibitory effects of potassium channel inhibitors on relaxation responses were comparable among the groups. The cystometric findings revealed that threshold and basal pressure values were higher in the hypercholesterolemia group compared with controls. We showed that hypercholesterolemia leads to greater relaxation responses to isoproterenol, appears to impair the braking function of M-2 cholinergic receptors on adrenoceptor-induced relaxations in the isolated detrusor muscle, and affects the voiding function in rats.