title: ANP gene expression in rat hearts during hypoxia.
abstract: It is unclear whether the increase in plasma atrial natriuretic peptide (ANP) concentration during hypoxia is due to direct, hypoxia-induced upregulation of ANP secretion in the heart, or to pressure overload of the right ventricle (RV) following hypoxia-induced pulmonary hypertension. To test the hypothesis that hypoxia leads to an early upregulation of the ANP gene, we examined the influence of acute and prolonged inspiratory hypoxia (6 h, 1 or 3 weeks) on the expression of ANP messenger ribonucleic acid (mRNA) in rat heart and compared the results with the expression of the ANP gene after acute pressure overload induced by experimental coarctation of the main pulmonary artery. As a molecular marker for hypertrophy we determined the ratio of alpha- and beta-myosin gene expression. Hypoxia increased systolic RV pressure from 20.0 +/- 1.6 mmHg to 27.8 +/- 1.6 mmHg (P < 0.01) and 41.6 +/- 2.1 mmHg (P < 0. 05) after 1 and 3 weeks hypoxia respectively. The ANP plasma concentration did not change significantly after 6 h or 1 week: 232 +/- 21 pg/ml (control), 246 +/- 25 pg/ml (6 h), 268 +/- 25 pg/ml (1 week), but increased significantly after 3 weeks hypoxia (446.8 +/- 99.56 pg/ml; P < 0.05). ANP mRNA levels in different regions of the heart did not change after 6 h or 1 week hypoxia. After 3 weeks hypoxia ANP mRNA had increased 2.7-fold in the RV (P < 0.05), 4. 2-fold in the left ventricle (LV, P < 0.05), 3.5-fold in the septum (S, P < 0.05) and about 1.4-fold in the right (n.s.) and left atrium (n.s.). Relative ventricular masses increased significantly only for the RV (190%, P < 0.05) during hypoxia. The beta/alpha-myosin mRNA ratio did not change after 6 h hypoxia but, contrary to ANP gene expression, increased after just 1 week (6.1-fold in RV, 7.8-fold in LV, 6-fold in S; P < 0.05) and was more pronounced in the RV after 3 weeks (9.4-fold in RV, 7.6-fold in LV, 9.1-fold in S; P < 0.05). The increase in the beta/alpha-myosin mRNA ratio in the LV contrasts with a lack of increase in relative ventricular mass. Acute pressure overload in the RV after pulmonary arterial banding significantly increased ANP-mRNA and the beta/alpha-myosin mRNA ratio after 1 day in the RV. In the LV ANP mRNA was unchanged. The delayed upregulation of the ANP gene suggests that hypoxia per se is not a significant stimulus for ANP gene expression in the heart and that hypoxia-induced ANP-gene expression in the heart is regulated predominantly by the increase in RV afterload due to hypoxia-induced increased pulmonary pressure. The upregulation of ANP and beta-myosin mRNA in the LV during chronic hypoxia has yet to be elucidated.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pfeifer
authors.forename: K
authors.initials: K
authors.lastname: Wolf
authors.forename: F C
authors.initials: FC
authors.lastname: Blumberg
authors.forename: D
authors.initials: D
authors.lastname: Elsner
authors.forename: F
authors.initials: F
authors.lastname: Muders
authors.forename: S R
authors.initials: SR
authors.lastname: Holmer
authors.forename: G A
authors.initials: GA
authors.lastname: Riegger
authors.forename: A
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001345:Autoradiography; D015870:Gene Expression / Q000235:genetics*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009320:Atrial Natriuretic Factor