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Published on: February 10, 2015
The effect of bile duct manipulation on cardiovascular responsiveness: in vivo studies
1Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa. bomzon@tx.technion.ac.il
Insights
The bile duct manipulated (BDM) rat model showed no changes in cardiovascular function or responsiveness compared to controls. These findings validate the BDM rat as a suitable control for cholestasis research.
Area of Science:
- Cardiovascular Physiology
- Hepatology
- Pharmacology
Background:
- Cholestasis, a condition of impaired bile flow, negatively impacts cardiovascular function.
- The bile duct manipulated (BDM) rat model was previously established for in vitro studies of cholestasis.
- The current study investigates the in vivo cardiovascular effects of the BDM model.
Purpose of the Study:
- To evaluate the effect of the bile duct manipulation (BDM) procedure on cardiovascular function and responsiveness in conscious rats.
- To validate the BDM rat as an appropriate control for in vivo studies of cholestasis.
Main Methods:
- Cardiovascular responsiveness was assessed in conscious BDM rats and control rats using head-up tilt, hemorrhage, and infusions of norepinephrine, tyramine, isoproterenol, angiotensin I, and angiotensin II.
- Plasma catecholamine concentrations and renin activity were measured in both groups.
Main Results:
- No significant differences in cardiovascular responsiveness were observed between BDM rats and control rats in response to any tested stimuli or drug infusions.
- Plasma catecholamine levels and renin activity were comparable between the BDM and control groups.
Conclusions:
- The bile duct manipulated (BDM) rat model does not alter in vivo cardiovascular function or responsiveness.
- These findings support the use of the BDM rat as a valid control group for future in vivo research on cholestasis-induced cardiovascular alterations.
Abstract:
Cholestasis depresses cardiovascular function and responsiveness. In a previous study, the 3-day bile duct manipulated (BDM) rat was validated as the appropriate control for studying in vitro vascular neuroeffector mechanisms in cholestasis. The present study reports the findings on the effect of BDM on cardiovascular function and responsiveness in conscious rats. Cardiovascular responsiveness was assessed by measuring the in vivo pressor responses to a 90 degrees head-up vertical tilt, a controlled hemorrhage, and to intravenously infused norepinephrine, tyramine, the indirectly acting sympathomimetic drug, isoproterenol, the nonselective beta-adrenoceptor agonist, angiotensin I, and angiotensin II. The concentrations of catecholamines and plasma renin activity measured in plasma samples obtained from conscious chronically arterial catheterized BDM rats were compared to identical data obtained from rats in which the bile duct was not manipulated. There were no differences in cardiovascular responsiveness to any of these procedures or drug infusions between the two groups of rats. Plasma catecholamine concentrations and renin activities in the BDM rats were not significantly different from control rats. Although no differences in cardiovascular responsiveness between BDM and control rats were observed, these data confirm the choice of the BDM as the control group for experiments assessing the effects of cholestasis on cardiovascular responsiveness.

