Selective vasodilator effects of atrial natriuretic peptide in the human placental vasculature.
OBJECTIVE
To determine whether atrial natriuretic peptide (ANP) attenuates the vasoconstrictor effects of angiotensin II (AII), a thromboxane mimetic (U46619), and endothelin-1 in the human fetal-placental vasculature and to determine whether nitric oxide (NO) has a role in the vasodilator activity of ANP.


METHODS
Isolated placental cotyledons were dually perfused, with fetal perfusion pressure used as an index of vascular response. The effects of AII (10(-10)-10(-6) mol/L bolus injection), endothelin-1 (10(-7) mol/L bolus), and U46619 (10(-9)-10(-6) mol/L bolus or 10(-8) mol/L infusion) were established in the absence or presence of ANP (10(-8) mol/L). The role of NO as a mediator of ANP action was investigated by perfusion with n-nitro-L-arginine (NNLA, 10(-3) mol/L), an inhibitor of NO synthase. Statistical significance was determined by analysis of variance.


RESULTS
Atrial natriuretic peptide caused significant attenuation of vasoconstrictor responses to AII, but weak attenuation of endothelin-1 and no attenuation of U46619. Use of NNLA did not affect the attenuation of AII-induced vasoconstriction by ANP.


CONCLUSIONS
Atrial natriuretic peptide is a vasodilator of the fetal-placental vasculature constricted with AII and endothelin-1, but not with U46619. Nitric oxide does not mediate the action of ANP.
Holcberg
G
G
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267-0526, USA.
Kossenjans
W
W
Brewer
A
A
Miodovnik
M
M
Myatt
L
L
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D005333:Fetus; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D019335:Nitroarginine / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D014664:Vasodilation / Q000187:drug effects*
D019332:Endothelin-1; D000804:Angiotensin II; D019335:Nitroarginine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009320:Atrial Natriuretic Factor