Cardiac responses to catecholaminare known to be attenuated in chronic liver disease. To elucidate the role of padrenergic receptor alteration in this phenomenon, we measured heart rate responsivenem to isoprenaline and myocardial p-adrenergic receptorbinding characteristics in three group of rate. thoee that were sham operated, those that had portal vein sten& and those that were cirrhotic because of bile duct ligation. Reeponeiveness to isoprenaline was evaluated in conscious rats by the dose of isoprenaline needed to increase b a d heart rate by 50 beats/min and by the maximal heart rate response. p-Receptor characteristics in heart membranes were derived from 'l'I-iodocyanopindolol binding data. Compared with sham-operated controls, cirrhotic rats needed a significantly higher dose of isoprenaline to raise basal heart rate by 50 beatslmin (102.3 f 19.1 vs. 28.3 f 11.3 ng/ltg) and lower maximal heart rate response (104 k 29 ~8 . 1 5 8 f 61 bea#min). In addition, myocardial preceptor denaity was signillcantly lower in cirrhotic rats (26.5 f 4.6 vs. 37.5 f 10.3 fmoUmgprotein) and the dissociation constant was higher (31.6 f 17.0 vs. 14.0 f 2.5 pmouL). Analyeis of pI& subpopulations revealed that the decreased total p-receptor density was entirely due to selective pl-receptor downregulation. p-Receptor atanity for ago& was not altered in cirrhotic rats. Rats with portal vein stenosis showed no signillcant differences in either isoprendine responsiveness or p-receptor characteristics when compared with controls. These resalte indicate that p-adrenergic receptor down-regulation may be responsible for the myocardial hyporesponeivenees to catecholamines observed in cirrhosis. (HEPAMIOW 1990;12:481-485.)
Patients with cirrhosis have attenuated cardiovascular responses to endogenous and exogenous catechola-