Hypotension in experimental cirrhosis. Is loss of vascular responsiveness to norepinephrine the cause of hypotension in chronic bile-duct-ligated dogs?
It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was studied in a dog model of portal hypertension and cirrhosis. Twelve weeks after bile duct ligation (n = 16), intrasplenic pressure rose significantly from 6.3 +/- 0.4 to 14.6 +/- 1.6 mmHg (p < 0.05), mean arterial pressure had fallen from 106 +/- 4 to 83 +/- 8 mmHg (p < 0.01), cardiac output had risen from 3.1 +/- 0.2 to 3.8 +/- 0.8 l/min (p < 0.05) and plasma norepinephrine concentrations rose from 0.22 +/- 0.12 to 1.17 +/- 0.52 nmol/l (p < 0.05). In 7 sham-operated dogs, the changes in these 4 variables over the same period were non-significant. In vivo pressor responsiveness was tested by studying the effects of intravenous and intra-arterial infusions of norepinephrine and the non-selective beta-adrenoceptor agonist, isoproterenol. In vitro responsiveness was tested by measuring the effects of isoproterenol on the isometric twitch of isolated ventricular strips and the effects of norepinephrine on femoral, mesenteric and renal arterial rings. There was no significant change in the in vivo responses of chronic bile-duct-ligated dogs at 12 weeks compared to the preoperative assessment, or to sham-operated dogs at 12 weeks. Furthermore, there was no significant difference between the in vitro responses of ventricular strips to isoproterenol or arterial rings to norepinephrine prepared from chronic bile-duct-ligated and sham-operated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Bomzon
A
A
Department of Pharmacology, Faculty of Medicine, Technion-Israel Institute of Technology Haifa, Israel.
Binah
O
O
Blendis
L M
LM
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001652:Bile Ducts / Q000502:physiology; D001663:Bilirubin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006975:Hypertension, Portal / Q000503:physiopathology; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000503:physiopathology*; D008111:Liver Function Tests; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D010953:Plasma Volume; D012016:Reference Values; D012083:Renin / Q000097:blood; D012709:Serum Albumin / Q000032:analysis; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary; D013997:Time Factors
D012709:Serum Albumin; D012982:Sodium, Dietary; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D012083:Renin; D007545:Isoproterenol; D001663:Bilirubin; D009638:Norepinephrine