title: Vascular alpha-adrenergic responsiveness is reduced in cirrhosis.
abstract: Cirrhosis of the liver is associated with altered cardiovascular regulation. Patients with cirrhosis often have decreased total peripheral vascular resistance despite increased sympathetic activity. To determine whether this reduction in effective sympathetic activity may be caused by an alteration in vascular adrenergic responsiveness, we studied nine patients with biopsy-proven cirrhosis and 12 age-matched control subjects. To assess human vascular adrenergic responsiveness, we used dorsal hand vein linear variable differential transformer techniques. Sensitivity for phenylephrine-mediated vasoconstriction was significantly reduced in patients with cirrhosis (median effective dose [ED50] for phenylephrine: cirrhosis, 1514 ng/min; control subjects, 282 ng/min; p = 0.026). In contrast, the effect of isoproterenol did not differ (cirrhosis: 89% +/- 15% of maximal nitroglycerin effect; control subjects 79% +/- 6%; ED50 for isoproterenol: cirrhosis, 38 ng/min; control subjects, 20 ng/min). These studies indicate that vascular alpha-adrenergic responsiveness in patients with cirrhosis is decreased, whereas beta-adrenergic responsiveness remains intact. A selective decrease in vascular alpha-adrenergic responsiveness may contribute to the decreased peripheral vascular resistance in cirrhosis.
authors.affiliation: Department of Medicine, University of Western Ontario, London, Canada.
authors.forename: G S
authors.initials: GS
authors.lastname: Bierbrier
authors.forename: P C
authors.initials: PC
authors.lastname: Adams
authors.forename: R D
authors.initials: RD
authors.lastname: Feldman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D007545:Isoproterenol