Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes

Abstract

The effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10(-9)-10(-6) mol/l, which corresponds to concentrations found in the plasma of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect.

Effects of Ursodeoxycholic Acid on Splanchnic and Systemic Hemodynamics

“…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].…”

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

“…In rats whose bile ducts have been ligated, the total bile acid concentration rises from 0.2pgml-' to about 200pgml-X (Bogin et al, 1983;Hardison et al, 1983). A previous electrophysiological study by Binah et al (1987) 'Si of the rat ventricular myocyte. In our study, NTC failed to modify the electrical activity of rabbit sino-atrial node at the physiological concentration range, but it exerted significantly depressant membrane actions at concentrations above 100pM.…”

“…Furthermore, Song et al (1983) demonstrated that sinus bradycardia is induced by obstructive jaundice. A recent in vitro study (Binah et al, 1987) showed that bile acids exert a negative inotropic effect mainly by a depression of Ca2+ influx of the cell membrane. Since Ca2 + conductance is predominantly responsible for the depolarization in sinoatrial node (Irisawa, 1978), a decrease in Ca2+ influx would alter the pacemaker spontaneous discharge.…”

Mechanism of bile salt vasoactivity: dependence on calcium channels in vascular smooth muscle

“…The cardiovascular effects of bile salts have been well described (Joubert, 1978;Bomzon et al, 1984;Binah et al, 1987;Pak & Lee, 1993), but few studies have examined their mechanism of action. The vasodilator effect of bile salts was confirmed in the present study using the isolated perfused mesentery.…”

“…Various theories have been proposed. Based on direct or circumstantial evidence, a role for membrane a-or Padrenoceptors (Joubert, 1978;Jacob et al, 1993), K+ channels (Binah et al, 1987), Na', K+-ATPase (Harries & I Author for correspondence. Sladen, 1971;Seda et al, 1984), endothelium-dependent relaxing factors (Lee et al, 1992), and sensory afferent fibres (Rozsa & Jacobson, 1989) in the mechanism of bile salt vasoactivity has been suggested.…”