Regulation of cardiac oxytocin system and natriuretic peptide during rat gestation and postpartum.
We have recently uncovered the presence of an oxytocin system in the heart and found that oxytocin is a physiological regulator of atrial natriuretic peptide (ANP), a diuretic, natriuretic and vasodilator cardiac hormone. However, dynamic changes in these systems during gestation, when mechanisms of volume and pressure homeostasis are altered, are not clear. Accordingly, ANP, oxytocin and oxytocin receptors were evaluated in rat hearts and plasma at three stages of gestation (7, 14 and 21 days) and at 2 and 5 days postpartum. Compared with non-pregnant controls, plasma ANP was elevated in mid-gestation, but significantly decreased at term (21 days), to increase again postpartum. Right and left atrial ANP mRNA levels were not altered throughout gestation but increased by 1.5- to 2-fold postpartum (P<0.01). At term, ANP content in right (8.7+/-1.2 vs 12.7+/-1.1 micro g/mg protein, P<0.04) and left (3.5+/-0.6 vs 8.5+/-2.0 micro g/mg protein, P<0.01) atria increased. These findings imply that decreased plasma ANP at term results from inhibition of release rather than decreased synthesis. In parallel, oxytocin, a stimulator of ANP release, decreased in left atria at day 7 to 50% of non-pregnant levels and remained low throughout gestation. Oxytocin receptor mRNA increased in left atria at 7 and 14 days of gestation by 2- and 5-fold respectively, but decreased at 21 days to lower than non-pregnant levels to increase again (3-fold) postpartum. The changes in oxytocin receptor expression at term and postpartum paralleled oxytocin receptor protein determined by Western blot. These results imply that pregnancy is associated with dynamic changes in the cardiac oxytocin system (peptide and/or receptors), which may influence natriuretic peptide release. Together, these peptides would act on their receptors in the heart, vasculature and kidneys to maintain vascular tone and renal function throughout gestation and postpartum.
Mukaddam-Daher
S
S
Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de l'Université de Montréal Research Center, Campus Hôtel-Dieu, Pavilion de Bullion 6-816, 3840 St-Urbain Street, Montréal, Québec H2W 1T8, Canada. suhayla.mukaddam-daher@umontreal.ca
Jankowski
M
M
Wang
D
D
Menaouar
A
A
Gutkowska
J
J
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006325:Heart Atria; D015151:Immunoblotting / Q000379:methods; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010121:Oxytocin / Q000032:analysis / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D010121:Oxytocin; D009320:Atrial Natriuretic Factor