Haemodynamic responses to a ring-deleted analogue of atrial natriuretic peptide in rats with cirrhosis.
OBJECTIVE
In cirrhosis, the effects of selective activation of atrial natriuretic peptide (ANP) R2-receptors on haemodynamics, endogenous ANP (ANP1-28) and sodium excretion are unknown. The aim of the present study was to examine the effects of selective activation of ANP-R2 receptors by ANP4-23 (a ring-deleted analogue of endogenous ANP) on haemodynamics, plasma ANP1-28 concentrations and urinary sodium excretion in conscious cirrhotic and normal rats.


METHODS
Haemodynamics and sodium excretion were measured prior to and following administration of ANP4 23. Plasma ANP1-28 concentrations were also measured.


RESULTS
In cirrhotic rats, ANP4-23 significantly decreased portal pressure and tributary blood flow by 15% and 25% respectively but significantly increased portal territory vascular resistance by 30%. Systemic and renal haemodynamics were not altered by ANP4-23. In normal rats, ANP4-23 did not significantly change splanchnic, renal and systemic haemodynamics. In both groups of rats, ANP4-23 increased plasma ANP1-28 concentrations but did not change sodium excretion.


CONCLUSIONS
ANP4-23 administration induced splanchnic vasoconstriction in cirrhotic but not in normal rats. ANP4-23-elicited vasoconstriction caused a portal hypotensive effect in cirrhotic rats. Finally, in both groups, ANP4-23 caused an increase in plasma ANP1-28 concentrations but did not increase sodium excretion.
Moreau
R
R
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-481, Hôpital Beaujon, Clichy, France.
Tazi
K A
KA
Komeichi
H
H
Pussard
E
E
Lebrec
D
D
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006975:Hypertension, Portal / Q000139:chemically induced / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D012964:Sodium / Q000652:urine; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology
D010446:Peptide Fragments; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C