title: The effect of hypercholesterolemia on carbachol-induced contractions of the detrusor smooth muscle in rats: increased role of L-type Ca2+ channels.
abstract: To investigate a possible relation between hypercholesterolemia and detrusor smooth muscle function, we studied the contractile response to potassium challenge, carbachol (CCh), and the components of CCh-induced contractile mechanism in high-cholesterol diet-fed rats. Adult male Sprague-Dawley rats were fed with standard (control group, N = 17) or 4 % cholesterol diet (hypercholesterolemia group (HC), N = 16) for 4 weeks. Spontaneous contractions of detrusor muscle strips and their responses to potassium chloride (KCl) or cumulative dose-contraction curves to CCh were recorded. The effects of muscarinic receptor antagonists (methoctramin and/or 4-diphenylacetoxy-N-methylpiperidine), L-type Ca(+2) channel blocker (nifedipine), and/or rho-kinase inhibitor Y-27632 were investigated. Blood cholesterol level was increased in the HC group with no sign of atherosclerosis. The KCl-induced detrusor smooth muscle contractions were higher in HC, whereas spontaneous and CCh-induced responses were similar in both groups. Preincubation with receptor antagonist for M(3) but not for M(2) attenuated contraction significantly, shifting the dose-response curve to the right. This response was similar in both groups. Among two effector mechanisms of M(3)-mediated detrusor smooth muscle contraction, rho-kinase pathway was not affected by hypercholesterolemia, whereas blockade of L-type Ca(+2) channels potently reduced contractions. The results of this study point out a relation between hypercholesterolemia and contractile mechanism of detrusor smooth muscle likely to change urinary bladder function, via altering L-type Ca(+2) channels. Taken together with escalating incidence of hypercholesterolemia and lower urinary tract symptoms, it is a field which deserves to be investigated further.
authors.affiliation: Department of Physiology, Faculty of Medicine, Hacettepe University, 39, Sihhiye, 06100, Ankara, Turkey.
authors.forename: Zeynep Dicle
authors.initials: ZD
authors.lastname: Balkanci
authors.forename: Bilge
authors.initials: B
authors.lastname: Pehlivanoğlu
authors.forename: Sibel
authors.initials: S
authors.lastname: Bayrak
authors.forename: Ismail
authors.initials: I
authors.lastname: Karabulut
authors.forename: Serkan
authors.initials: S
authors.lastname: Karaismailoğlu
authors.forename: Ayşen
authors.initials: A
authors.lastname: Erdem
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006937:Hypercholesterolemia / Q000503:physiopathology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000577:Amides; D020746:Calcium Channels, L-Type; D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D011725:Pyridines; D011976:Receptors, Muscarinic; C108830:Y 27632; D011189:Potassium Chloride; D002217:Carbachol; D009543:Nifedipine