Blunted systemic, splanchnic, and renal hemodynamic responses to atrial natriuretic peptide in rats with cirrhosis.
Systemic, splanchnic and renal hemodynamic responses to saline, physiological (25 ng.kg-1.min-1) and pharmacological (100, 300 and 600 ng.kg-1.min-1) doses of alpha human atrial natriuretic peptide were measured in normal (n = 7 for saline and 7-8 for each dose of atrial natriuretic peptide) and cirrhotic (n = 7 for saline and 7-8 for each dose of atrial natriuretic peptide), conscious, unrestrained rats. In addition, plasma norepinephrine concentrations were measured in normal and cirrhotic rats, before and following a 300-ng.kg-1.min-1 dose of atrial natriuretic peptide. In cirrhotic rats, splanchnic, renal and systemic hemodynamics were not significantly affected by either physiological or pharmacological doses of atrial natriuretic peptide. In normal rats, a 300 ng.kg-1.min-1 dose of atrial natriuretic peptide significantly decreased cardiac index, portal tributary blood flow and renal blood flow, and significantly increased vascular resistance in the systemic, portal, and renal territories. The other doses of atrial natriuretic peptide did not significantly change regional and systemic hemodynamics. Atrial natriuretic peptide-induced changes in plasma norepinephrine concentrations were significantly higher in normal than in cirrhotic rats (1827 +/- 834 vs. 59 +/- 46 pg/ml, mean +/- S.E., respectively). In conclusion, this study shows that the normal cardiovascular response to a 300 ng.kg-1.min-1 atrial natriuretic peptide infusion is blunted in cirrhotic rats. Moreover, in cirrhotic rats, blunting of vasoconstriction following atrial natriuretic peptide administration seems to be due to a lack of increased sympathetic vascular tone.
Ohsuga
M
M
Laboratoire d'Hémodynamique Splanchnique, INSERM U-24, Hôpital Beaujon, Clichy, France.
Moreau
R
R
Hartleb
M
M
Komeichi
H
H
Lebrec
D
D
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D012965:Sodium Chloride / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects*
D004232:Diuretics; D010446:Peptide Fragments; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D009638:Norepinephrine