ANGIOTENSIN-II RECEPTOR SUBTYPES IN THE ADRENALS OF PREGNANT RATS

During human and rat pregnancy, several hemodynamic and endocrine processes are markedly modified. These include activation of the renin-angiotensin system (RAS) and increase of plasma aldosterone. However, the rise of plasma aldosterone is greater than expected from the elevation of RAS activity. Gestational alterations in angiotensin II receptors (AT receptor) in the adrenal could explain this apparent hyperaldosteronism. This study was conducted to determine differences between AT receptor subtypes in the adrenal glands of non-pregnant and pregnant (22 days) rats. Using plasma membrane preparations from adrenal glomerulosa and medulla, we determined receptor density and affinity with I-125-angiotensin II(ANG II); the AT receptor subtypes were assessed by displacement of I-125-ANG II binding with subtype-specific antagonists (DuP753 and PD123319). In zona glomerulosa of non-pregnant and pregnant rats, AT(1) receptors predominated(approximate to 80%) with no statistical difference in receptor density (B-max) and affinity (K-d) and the ratio of receptor subtypes between the two groups of rats. In adrenal medulla of both groups of rats, the major portion of I-125-ANG II binding (60-70%) was displaced by the AT(1) receptor antagonist, PD123319. Neither B-max nor K-d differed in this tissue during gestation. The results for AT(1) receptor density were confirmed by Western blot. Northern blot analysis showed that AT(1) mRNA level in the adrenal is not modified by gestation. These results indicate that the number, the affinity and the transcription of the AT(1) receptor in the adrenal are not altered during pregnancy, indicating that the rise in aldosterone secretion during pregnancy could not be explained by increase of AT(1) receptors in the zona glomerulosa, or modification of AT(1)/AT(2) ratio.