Systemic hypotension and pressor responsiveness in cholestasis. A study in conscious 3-day bile duct ligated rats

It has been postulated that the physiological basis for systemic hypotension in cholestatic liver disease is the attenuated responsiveness of the cardiovascular system to sympathetic stimulation. Using conscious 3-day bile duct ligated rats, we tested this hypothesis by measuring the vasopressor and vasodilator responses following intravenous infusions of norepinephrine, tyramine, angiotensin II, angiotensin I and isoproterenol, in conjunction with the pressor responses to a head-up vertical tilt and a controlled hemorrhage. The results were compared to those obtained in conscious sham-operated rats. Bile duct ligation reduced the mean arterial blood pressure without a significant increase in heart rate. The pressor responses to the aforementioned drugs obtained in the bile-duct ligated rats were significantly attenuated from those the sham-operated rats. In contrast, bile duct ligation had no effect on the pressor responses to tilting and hemorrhage when compared to the responses obtained in the sham-operated rats. Despite the presence of systemic hypotension and attenuation of pressor response to vasoactive drugs, the ability of the cardiovascular system to respond to physiological stimuli appears to be intact in this model. Therefore, we conclude that blunted pressor responsiveness of the cardiovascular system is probably not an important physiological determinant of systemic hypotension in cholestatic liver disease.