Effect of bile acid on electrophysiological properties of rabbit sino‐atrial node <i>in vitro</i>

Kotake, Hiroshi; Itoh, Takuzì; Watanabe, Masashi; Hisatome, Ichiro; Hasegawa, Junichi; Mashiba, Hiroto

doi:10.1111/j.1476-5381.1989.tb12604.x

Cited by 23 publications

(17 citation statements)

References 24 publications

(27 reference statements)

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“…This resulted in a slight but insignificant reduction in MAP, similar to recent findings from cirrhotic patients [14]. The decrease in DBP was not related to any impairment in the function of the myocardium or the sino-atrial node, as previously described for hydrophobic bile acids [15, 16]. The reduction in DBP may be caused either by a vasodilative effect of UDCA or by an impaired response to vasopressive mediators, as described for other bile acids like taurocholate [17, 18].…”

Section: Discussionsupporting

confidence: 73%

Effects of Ursodeoxycholic Acid on Splanchnic and Systemic Hemodynamics

et al. 2000

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Background: Recently, the beneficial effects of ursodeoxycholic acid (UDCA) on the portal hypertensive state have been demonstrated in patients with primary biliary cirrhosis. However, it is not known whether UDCA has direct or indirect effects on the vascular smooth muscles in humans, thereby leading to a change in splanchnic or systemic hemodynamics. Aims: We therefore evaluated the hemodynamic effects of UDCA as to its established effect on gallbladder motility under fasting and postprandial conditions in healthy volunteers. Methods: In a double-blind, cross-over study of 20 healthy volunteers, placebo or UDCA (750 mg/d) were randomly administered over 4 weeks with an interim 4-week washout period. Portal blood flow, cardiac output and gallbladder motility were measured using echo-Doppler and b-mode sonography before and after placebo and verum, respectively. ECG, blood pressure, heart rate and blood chemistry were also measured. Results: UDCA did not significantly change fasting portal flow or meal-induced portal hyperemia. Both fasting and postprandial gallbladder volumes increased (26.5 ± 6.0 vs. 40.7 ± 13.8 ml, p < 0.05, and 11.2 ± 6.2 vs. 14.8 ± 6.7 ml, p < 0.05). Diastolic blood pressure decreased under UDCA (71.2 ± 8.7 vs. 66.5 ± 6.5 mm Hg, p < 0.05). Serum levels of chloride and γ-glutamyltransferase decreased slightly, while alkaline phosphatase increased. Conclusions: UDCA affected systemic but not portal hemodynamics. The increase in gallbladder volume is obviously mediated by factors that do not influence the splanchnic vascular bed.

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Section: Discussionsupporting

confidence: 73%

Effects of Ursodeoxycholic Acid on Splanchnic and Systemic Hemodynamics

et al. 2000

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“…This hypothesis was evaluated in one publication by Kotake et al [8] in which it was noted that bile acids affected the sinoatrial node by depressing node action potentials in a dose-related manner and producing a negative chronotropic effect which leads to bradycardia. In agreement with previous research results, another report indicated that taurocholate, another bile acid, caused a decrease in the rate of contraction of rat cardiomyocytes [23].…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence has emerged to indicate that bile acids have arrhythmogenic potential [6,7]. It has been observed that increasing the concentration of bile acids alters the sinoatrial node and induces bradycardia [8]. This mechanism might explain acute fetal death because an association with a chronic cause, such as placental insufficiency, has not been demonstrated [9,10].…”

Section: Introductionmentioning

confidence: 99%

Increased PR Interval in Fetuses of Patients with Intrahepatic Cholestasis of Pregnancy

et al. 2016

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Objective: To evaluate the fetal mechanical PR interval in fetuses from pregnancies with intrahepatic cholestasis of pregnancy (ICP). Methods: A case-control study was conducted in the Maternal-Fetal Medicine Unit at Hospital Carlos Van Buren between 2011 and 2013. Fetal echocardiography was performed in patients with ICP and normal pregnancies. Demographic and clinical characteristics were compared using the Mann-Whitney U test for continuous variables. A p value <0.05 was considered significant. Results: 51 patients with ICP were compared with 51 unaffected pregnancies. There were no significant differences in neither demographic nor clinical characteristics between the two groups. The fetal PR interval was significantly longer in the ICP group when compared to the control group (134.6 ± 12 vs. 121.4 ± 10 ms, p < 0.001). Moreover, four fetuses from the ICP group had a mechanical PR interval >150 ms, which is compatible with a first-degree atrioventricular block. Two fetuses were identified in the neonatal period and were transferred to pediatric cardiology for follow-up, with a normal mechanical PR after the first month of life. Conclusions: We demonstrated that the fetal cardiac conduction system is altered in fetuses of patients with ICP. Further research is necessary to determine whether this alteration is related to stillbirths seen in ICP.

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“…The activation of BK Ca channels has been reported to control membrane potential and the degree of contraction and/or contractility in both vascular (Brayden and Nelson, 1992;Asano et al, 1993;Jaggar et al, 2000) and nonvascular (SuarezKurtz et al, 1991;Anwer et al, 1993) smooth muscle. Previous studies that showed bile acid-induced increases in K ϩ currents were performed in nonsmooth muscle preparations (Binah et al, 1987;Kotake et al, 1989;Devor et al, 1993). In particular, an increase in a Ca 2ϩ -sensitive conductance in colonic secretory cells by taurodeoxycholic acid led Dharmsathaphorn et al (1989) to postulate an involvement of Ca 2ϩ -dependent K ϩ channels in taurodeoxycholic acid effects on secretion in these cells.…”

Section: Possible Role Of Bile Acid Activation Of Bk Ca Channels In Bmentioning

confidence: 99%

Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells

Dopico

2002

The Journal of General Physiology

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Bile acids have been reported to produce relaxation of smooth muscle both in vitro and in vivo . The cellular mechanisms underlying bile acid-induced relaxation are largely unknown. Here we demonstrate, using patch-clamp techniques, that natural bile acids and synthetic analogues reversibly increase BK Ca channel activity in rabbit mesenteric artery smooth muscle cells. In excised inside-out patches bile acid-induced increases in channel activity are characterized by a parallel leftward shift in the activity-voltage relationship. This increase in BK Ca channel activity is not due to Ca 2 ϩ -dependent mechanism(s) or changes in freely diffusible messengers, but to a direct action of the bile acid on the channel protein itself or some closely associated component in the cell membrane. For naturally occurring bile acids, the magnitude of bile acid-induced increase in BK Ca channel activity is inversely related to the number of hydroxyl groups in the bile acid molecule. By using synthetic analogues, we demonstrate that such increase in activity is not affected by several chemical modifications in the lateral chain of the molecule, but is markedly favored by polar groups in the side of the steroid rings opposite to the side where the methyl groups are located, which stresses the importance of the planar polarity of the molecule. Bile acidinduced increases in BK Ca channel activity are also observed in smooth muscle cells freshly dissociated from rabbit main pulmonary artery and gallbladder, raising the possibility that a direct activation of BK Ca channels by these planar steroids is a widespread phenomenon in many smooth muscle cell types. Bile acid concentrations that increase BK Ca channel activity in mesenteric artery smooth muscle cells are found in the systemic circulation under a variety of human pathophysiological conditions, and their ability to enhance BK Ca channel activity may explain their relaxing effect on smooth muscle.

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Effect of bile acid on electrophysiological properties of rabbit sino‐atrial node in vitro

Cited by 23 publications

References 24 publications

Effects of Ursodeoxycholic Acid on Splanchnic and Systemic Hemodynamics

Effects of Ursodeoxycholic Acid on Splanchnic and Systemic Hemodynamics

Increased PR Interval in Fetuses of Patients with Intrahepatic Cholestasis of Pregnancy

Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells

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