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.

Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring

“…To determine mechanisms underlying the increased pressor and vascular tone, we focused on resistance arteries and ion channels on smooth muscle cells. Numerous studies showed physiopathologic basis of vascular disorders involving dysfunction of L-type Ca 2+ channels, e.g, an up-regulation of LTCCs in the genesis of hypertension and hypercholesterolemia 36 38 39 . Recently, our colleagues demonstrated that high-sucrose diets in pregnancy altered angiotensin II-mediated pressor responses and vessel tone via PKC/Cav1.2 pathway 40 .…”

The effect of hypercholesterolemia on the contractions of detrusor strips in response to neural stimulation in rats

“…Twelve male SpragueDawley rats of 4-7 weeks old were divided into control (n = 6) and cholesterol (n = 6) groups. The control group (NC) was fed with standard rat chow and the cholesterol group (HC) was fed with a high cholesterol diet (4% cholesterol and 0.2% deoxycholate) for 4 weeks (22,23). All rats were kept in standard conditions (room temperature in a 12-h light/12-h dark cycle) with free access to food and water.…”

Hypercholesterolemia Effect on Potassium Channels

“…High-cholesterol diet-induced hypercholesterolemia is widely used for studies on monkeys [42], hamsters [43], guinea pigs [44], rabbits [20,27,29,45,46], rats [19,[47][48][49] and mice [50]. The dietary-induced hypercholesterolemia model has several advantages.…”