Prolonged antagonism of alpha 1-adrenergic vasoconstriction in the rat liver by atrial natriuretic peptide.
OBJECTIVE
Vasodilator hormones that regulate hepatic circulation at physiological concentrations have not been sufficiently identified. The presence of atrial natriuretic peptide (ANP) and its receptors in the hepatic vascular bed suggest such vasorelaxing potential.


METHODS
Livers of male Sprague-Dawley rats were perfused in a flow-constant fashion. The selective alpha 1-adrenergic agonist phenylephrine (PE) (1.5 mumol/L) was infused from 30 to 36 minutes and again from 70 to 76 minutes after starting perfusion (n = 5). ANP (0.1 pmol/L to 200 nmol/L), des-(Gln18, Ser19, Gly20, Leu21, Gly22)-ANP fragment (C-ANP) (20 nmol/L), or 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) (50 mumol/L) (each n = 4) were added from 20 to 40 minutes.


RESULTS
During the first infusion of PE, portal pressure increased from 3.7 +/- 0.5 to 12.1 +/- 0.8 cm H2O maximally (mean +/- SD) and increased again to 11.5 +/- 2.0 during the second PE infusion. ANP at physiological concentrations reduced both PE-induced increases of portal pressure in a dose-dependent fashion, reaching half-maximal effects around 20 pmol/L and maximal effects (about 50% inhibition of PE-induced vasoconstriction) at 40 pmol/L. The cGMP analogue 8-Br-cGMP showed the same long-lasting vasodilating effect as ANP. In contrast, C-ANP, which binds only to the ANP C-receptor, had no effects.


CONCLUSIONS
Physiological concentrations of ANP antagonize alpha 1-adrenergic vasoconstriction in the liver, suggesting an important function in the humoral regulation of hepatic circulation. The prolonged hemodynamic effect of ANP seems to be ANP A-receptor/guanylyl cyclase/cGMP-mediated.
Bilzer
M
M
Second Department of Medicine, Klinikum Grosshadern, University of Munich, Germany.
Paumgartner
G
G
Gerbes
A L
AL
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000819:agonists; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP