Estrogen receptors activate atrial natriuretic peptide in the rat heart

Abstract

In this study, semiquantitative reverse transcription-PCR analysis showed that estrogen receptor ␣ (ER␣) and ␤ (ER␤) mRNAs are developmentally regulated in the rat heart. We found that ER␣ mRNA was low in all heart chambers of 4-day-old rats, but was elevated in the atria (6-to 18-fold) and ventricles (3-to 4-fold) of adult rats. Western blotting analysis confirmed that these differences were efficiently translated into 67-kDa ER␣ protein. ER␤ mRNA was expressed at its highest level in the left atrium and was 3-to 4-fold lower in other heart chambers of 4-day-old animals. In adult rats ER␤ was decreased dramatically in the left atrium (20-fold) and, to a lesser extent in the other heart chambers (2-to 4-fold). Significant ER changes occurred already in the first week after birth. Accordingly, estrogen regulation in cells from neonatal hearts, as reported in several studies, may not correspond to that occurring in fully differentiated adult hearts, because of an altered degree of ER expression. In adult rats, ovariectomy decreases atrial ER␣, the atria͞body weight ratio, and atrial natriuretic peptide (ANP) transcription. Treatment of ovariectomized rats with 17-␤-estradiol (25 g, 10 days, s.c.) reversed these changes. In addition, there was no effect of ovariectomy and 17-␤-estradiol supplementation on systolic blood pressure, but in ovariectomized rats a decreased heart rate followed 17-␤-estradiol administration. Similar to the effects on ER␣ in the atria, ovariectomy lowered plasma ANP levels, and 17-␤-estradiol administration restored ANP in the plasma of ovariectomized rats. Changes in plasma ANP correlated with changes in ANP content in the right atrium, as demonstrated by RIA. Increased ANP expression and secretion in response to ER␣ activation may be a protective mechanism in the heart. A trial natriuretic peptide (ANP) is a cardiac hormone produced predominantly in heart atria (1). It acts primarily on the ANP A receptor, that is, guanylyl cyclase, which converts GTP to cGMP. cGMP mediates the actions of ANP via protein kinase G. ANP plays an integral role in the regulation of hydromineral homeostasis under normal and pathological conditions, through potent biological effects, including vasorelaxation, diuresis, natriuresis, and reduction of venous return by a shift of plasma into the interstitium. The natriuretic and diuretic actions of ANP result from enhanced glomerular filtration and͞or decreased tubular reabsorption of sodium and water, suppression of renin, aldosterone, and vasopressin secretion, as well as antagonism of most of the peripheral and central effects of angiotensin II. The heart not only secretes ANP but also expresses ANP receptors, which control heart functions through cGMP production in cardiomyocytes and fibroblasts (2).The ANP gene is strongly activated in response to hypertrophic stimuli in the heart and prevents hypertrophy by inhibition of protein synthesis in cardiac myocytes via a cGMP-dependent process (3). Mice lacking ANP or its guanylyl cyclase A receptor exhibit marked ...

Neonatal oxytocin treatment modulates oxytocin receptor, atrial natriuretic peptide, nitric oxide synthase and estrogen receptor mRNAs expression in rat heart

“…We observed that ERα expression rises from low levels on postnatal D1, whereas ERβ mRNA decreases by postnatal D21 in the rat heart, suggesting a specific role for both receptors in heart maturation. These results are in agreement with previous study in which high ERβ expression was observed in the newborn heart and at 4 days of postnatal life [23], when extensive hyperplasia of the rat heart occurs and the heart grows more rapidly than the body [11]. In adult rats, ERβ expression is low, in contrast to relatively high ERα mRNA levels.…”

Arginine Vasopressin-mediated Cardiac Differentiation

“…Because a maximal response was observed for treatment with 10 Ϫ7 M AVP, this concentration was used throughout the study. (12).…”

Regulation of cardiac oxytocin system and natriuretic peptide during rat gestation and postpartum

“…A similar procedure was applied for amplification of rat ANP mRNA and for 18S mRNA, used as internal standard for semiquantitative gene expression analysis (Jankowski et al 2001). Control RT-PCRs were conducted by omitting reverse transcriptase or RNA from the reaction mixture.…”

“…The actions of estrogen and progesterone are mediated by specific-binding sites present in vascular tissue (Taylor & Al-Azzawi 2000, Critchley et al 2001 and heart (Jankowski et al 2001), through stimulation of endothelial nitric oxide and cGMP (Darkow et al 1997, Rosenfeld et al 2000, and through stimulation of the release and/or synthesis of cardiac natriuretic peptides and oxytocin.…”

“…In sheep, plasma ANP increases early and remains elevated throughout gestation (Mukaddam-Daher et al 1994) and in vivo atrial stretch-induced ANP release is stimulated during pregnancy (Javeshghani et al 1995). In the rat, chronic treatment with estradiol increases ANP release from isolated atria (Kaufman 1995), stimulates atrial ANP mRNA, and increases plasma ANP levels (Jankowski et al 2001). However, during rat gestation, plasma ANP decreases at term to lower than non-pregnant levels, despite elevated estradiol levels, which would suggest that factors other than estradiol may be involved in ANP release in rat pregnancy.…”