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.

The NO donor molsidomine reduces endothelin-1 gene expression in chronic hypoxic rat lungs

“…Experimental groups and chronic hypoxia. Adult male Wistar rats (250-300 g; Charles River, Sulzfeld, Germany) were randomly assigned to one of the following groups: normoxia and plain water from Rats were exposed to normobaric hypoxia (10% O 2 -90% N 2 ) in transparent plastic chambers as previously described (20). Relative humidity within the chamber was kept at Ͻ70% with anhydrous CaSO 2 .…”

“…At the end of the study period, right ventricular systolic pressure (RVSP) was measured in all rats with a closed-chest technique as previously described (20). For this purpose, each rat was taken from its cage and immediately anesthetized with thiopental sodium (50 mg/kg ip).…”

Endothelial actions of atrial natriuretic peptide prevent pulmonary hypertension in mice

“…Experimental and clinical studies showed that during chronic hypoxia, right heart ANP and BNP synthesis and circulating NP levels increase, possibly in response to the RV pressure overload provoked by pulmonary vasoconstriction [ 9 – 11 , 44 ]. Because synthetic ANP counterregulates hypoxic pulmonary vasoconstriction [ 8 , 22 , 26 ] and limits the interaction of endothelial and inflammatory cells [ 25 , 39 ] and the proliferation of cultured vascular SMC [ 24 ], it was proposed that enhanced endogenous ANP/BNP release helps to mitigate the development of hypoxic PH [ 9 , 10 ].…”

Maternal methamphetamine administration during pregnancy influences on fetal rat heart development

“…CA itself stimulates the a 1 -adrenergic receptor and then up-regulated h-MHC mRNA expression and, thereby, myocardial hypertrophy (Waspe et al, 1990;Kariya et al, 1993Kariya et al, , 1994Morkin, 2000). Furthermore, h-MHC mRNA expression is up-regulated under certain conditions, including pressure overload and hypoxia (Gupta and Gupta, 1997;Pissarek et al, 1997;Wong et al, 1997;Pfeifer et al, 1997;Morkin, 2000;Joseph et al, 2000). It may be that the decrease in the plasma levels of progesterone indicated an impairment of the functions of the placenta, and that fetal hypoxia occurred.…”