Characteristics of ANP-binding sites in the adrenal capsules of term-pregnant rats.
Significant increases of circulatory volume and plasma aldosterone levels are observed in pregnancy. We investigated whether a decrease of atrial natriuretic peptide (ANP) receptors in the adrenal zona glomerulosa (ZG) could explain the marked elevation of plasma aldosterone occurring during pregnancy. 125I-ANP binding was measured in competition experiments using rANP(1-28), ANP(4-23), a truncated analog which has high specificity for the ANP-C receptor, or a combination of both. Western blot experiments were also performed with an investigation into the effect of ANP on aldosterone secretion in adrenal capsule suspensions. 125I-ANP binding on adrenal ZG membranes was displaced by ANP(1-28) with an affinity (Kd) of 313 +/- 39 and 323 +/- 60 pM (NS) for pregnant and non-pregnant rats, respectively. The density of sites (Bmax) decreased slightly but not significantly during pregnancy. Displacement experiments with ANP(4-23) demonstrated a Bmax of 137 and 134 fmol/mg of proteins (NS) for pregnant and non pregnant rats, respectively. Studies were performed to block the ANP-C site. Displacing the remaining 125I-ANP binding with ANP(1-28) led to an affinity constant and receptor density which were not significantly different between the two groups of rats. The results obtained with Western blots showed a single band of 123 kDa with no significant variations in ANP-R1 receptors in the ZG during gestation. The sensitivity of potassium-, ACTH- or angiotensin II-stimulated aldosterone secretion to ANP was not altered by gestation. These data show that the apparent hyperaldosteronism found in normal term-pregnant rats is not the consequence of modifications in the affinity, number and properties of ANP receptor types or in the sensitivity of the aldosterone response to ANP.
Forcier
I
I
Centre de recherche, Hôpital Sainte-Justine, Montreal, Quebec, Canada.
St-Louis
J
J
Brochu
M
M
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001665:Binding Sites; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
D010446:Peptide Fragments; C472610:atrial natriuretic peptide, rat; D000804:Angiotensin II; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D011188:Potassium