Lack of vascular hyporesponsiveness to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis

Background/Aims: In cirrhosis, the mechanism(s) for vascular hyporesponsiveness to vasoconstrictors such as, α1-adrenoceptor agonists, vasopressin and angiotensin II, are unclear. Moreover, vascular reactivity to substances such as L-type calcium channel activators is unknown. Methods: Thus, presor dose-response curves to vasoconstrictors [phenylephrine (an α1-agonist, 0.1–500 μgg/kg) angiotensin II (10–500 ng/kg), vasopressin (0.01–5 IU/kg), and Bay K 8644 (an L-type calcium channel activator, 0.5–50 μg/kg] were obtained in normal rats and in rats with secondary biliary cirrhosis. All experiments were performed in ganglionic-blocked animals to limit the influence of cardiovascular reflexes. Doses of vasoconstrictor necessary to obtain 40 mmHg increase in arterial pressure (D40) were calculated. Results: Compared to normal animals, rats with cirrhosis had significantly higher D40 values for angiotensin II (171±57 vs. 344±41 ng/kg), phenylephrine (2.6±0.2 vs. 26.4±10.7 μg/kg) and vasopressin (73±19 vs. 401±150 mU/kg). Pressor responses to Bay K 8644 did not differ between normal rats and rats with cirrhosis (8.8±0.9 vs. 10.5±2.1 μg/kg). Conclusions: In conclusion, this study shows that cirrhosis produces vascular hyporeactivity to phenylephrine, vasopressin and angiotensin II but not to Bay K 8644. Therefore, cirrhosis impairs certain constrictor mechanisms which are shared by phenylephrine, angiotensin II and vasopressin but which do not contribute to the vascular response to Bay K 8644.