Lack of vascular hyporesponsiveness to the L-type calcium channel activator, Bay K 8644, in rats with cirrhosis.
OBJECTIVE
In cirrhosis, the mechanism(s) for vascular hyporesponsiveness to vasoconstrictors such as, alpha 1-adrenoceptor agonists, vasopressin and angiotensin II, are unclear. Moreover, vascular reactivity to substances such as L-type calcium channel activators is unknown.


METHODS
Thus, pressor dose-response curves to vasoconstrictors [phenylephrine (an alpha 1-agonist, 0.1-500 micrograms/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 micrograms/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 a 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 micrograms/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 micrograms/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.
Hartleb
M
M
Laboratoire d'Hémodynamique Splanchnique, INSERUM U-24, Hôpital Beaujon, Clichy, France.
Moreau
R
R
Gaudin
C
C
Lebrec
D
D
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005730:Ganglionic Blockers / Q000494:pharmacology; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000494:pharmacology
D015220:Calcium Channels; D005730:Ganglionic Blockers; D014667:Vasopressins; D000804:Angiotensin II; D010656:Phenylephrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester