Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

In low sodium-induced intrauterine growth restricted (IUGR) rat, foetal adrenal steroidogenesis as well as the adult renin–angiotensin–aldosterone system (RAAS) is altered. The aim of the present study was to determine the expression of cytochrome P450 aldosterone synthase (P450aldo) and of angiotensin II receptor subtypes 1 (AT1R) and 2 (AT2R) in adult adrenal glands and whether this expression could be influenced by IUGR and by high-salt intake in a sex-specific manner. After 6 weeks of 0.9% NaCl supplementation, plasma renin activity, P450aldo expression and serum aldosterone levels were decreased in all groups. In males, IUGR induced an increase in AT1R, AT2R, and P450aldo levels, without changes in morphological appearance of the zona glomerulosa (ZG). By contrast, in females, IUGR had no effect on the expression of AT1R, but increased AT2R mRNA while decreasing protein expression of AT2R and P450aldo. In males, salt intake in IUGR rats reduced both AT1R mRNA and protein, while for AT2R, mRNA levels decreased whereas protein expression increased. In females, salt intake reduced ZG size in IUGR but had no affect on AT1R or AT2R expression in either group. These results indicate that, in response to IUGR and subsequently to salt intake, P450aldo, AT1R, and AT2R levels are differentially expressed in males and females. However, despite these adrenal changes, adult IUGR rats display adequate physiological and adrenal responses to high-salt intake, via RAAS inhibition, thus suggesting that extra-adrenal factors likely compensate for ZG alterations induced by IUGR.

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High‐salt intake up‐regulation of AT1 and AT2 protein expression in the left ventricle is independent of blood pressure

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.968.14 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Daniele Nunes Ferreira ◽

Michella Soares Coelho ◽

Ivone Braga Oliveira ◽

Kaleizu T. Rosa ◽

Joel C. Heimann

Keyword(s):

Blood Pressure ◽

Left Ventricle ◽

Protein Expression ◽

Salt Intake ◽

High Salt ◽

High Salt Intake

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High salt intake attenuates antihypertensive action of angiotensin II receptor blockade with induction of renal oxidative stress

The FASEB Journal ◽

10.1096/fasebj.20.4.a755-a ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Satoshi Endo ◽

Takefumi Mori ◽

Yoshimi Yoneki ◽

Goro Tokudome ◽

Tatsuo Hosoya ◽

...

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Salt Intake ◽

High Salt ◽

Receptor Blockade ◽

Angiotensin Ii Receptor ◽

Antihypertensive Action ◽

High Salt Intake ◽

Angiotensin Ii Receptor Blockade

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Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00387.2011 ◽

2012 ◽

Vol 302 (9) ◽

pp. R1025-R1033 ◽

Cited By ~ 5

Author(s):

Qing Wang ◽

Andrea A. Domenighetti ◽

Stephan C. Schäfer ◽

Johanns Weber ◽

Alexandra Simon ◽

...

Keyword(s):

Gene Expression ◽

Cardiac Hypertrophy ◽

Protein Expression ◽

Vascular Remodeling ◽

Salt Intake ◽

High Salt ◽

Cardiovascular Remodeling ◽

High Salt Intake ◽

Gene And Protein Expression ◽

Differential Gene

We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt-induced cardiac hypertrophy in the absence of hypertension in one-renin gene mice. This model allows us to study molecular mechanisms of high-salt intake in the development of cardiovascular remodeling, independently of blood pressure in a high mineralocorticoid state. In this study, we compared the effect of 5-wk low- and high-salt intake on cardiovascular remodeling and cardiac differential gene expression in mice receiving the same amount of DOCA. Differential gene and protein expression was measured by high-density cDNA microarray assays, real-time PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice. DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and left ventricular dysfunction. Differential gene and protein expression demonstrated that high-salt intake upregulated a subset of genes encoding for proteins involved in inflammation and extracellular matrix remodeling (e.g., Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded for transcription factors, including myeloid differentiation primary response (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis, and inflammation are important consequences of a high-salt intake in DOCA mice. Our study suggests that among the different pathogenic factors of cardiac and vascular remodeling, such as hypertension and mineralocorticoid excess and sodium intake, the latter is critical for the development of the profibrotic and proinflammatory phenotype observed in the heart of normotensive DOCA-treated mice.

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High salt intake induces collecting duct HDAC1-dependent NO signaling

AJP Renal Physiology ◽

10.1152/ajprenal.00323.2020 ◽

2020 ◽

Author(s):

Randee S Sedaka ◽

Kelly A. Hyndman ◽

Elena Mironova ◽

James D Stockand ◽

Jennifer S Pollock

Keyword(s):

Salt Intake ◽

Ex Vivo ◽

Collecting Duct ◽

High Salt ◽

No Production ◽

Mrna Levels ◽

No Donor ◽

Histone Deacetylase 1 ◽

High Salt Intake ◽

Endothelin B

We reported that high salt intake stimulates renal collecting duct (CD) endothelin B receptor (ETBR)/NOS1β-dependent NO production inhibiting the epithelial sodium channel (ENaC) promoting natriuresis. However, the mechanism underlying the high salt (HS) induced increase of NO production is unclear. Histone deacetylase 1 (HDAC1) responds to increased fluid flow, as can occur in the CD during HS intake. The renal inner medulla (IM), in particular the IMCD, has the highest NOS1 activity within the kidney. Hence, we hypothesized that HS intake provokes HDAC1 activation of NO production in the IM. HS intake for one week significantly increased HDAC1 abundance in the IM. Ex vivo treatment of dissociated IM from HS mice with a selective HDAC1 inhibitor (MS-275) decreased NO production with no change in endothelin-1 (ET-1) peptide or mRNA levels. We further investigated the role of the ET-1/ETBR/NOS1β signaling pathway with chronic ETBR blockade (A-192621). Although NO was decreased and ET-1 levels were elevated in dissociated IM from HS mice treated with A-192621, ex vivo MS-275 did not further change NO or ET-1 levels suggesting that HDAC1 mediated NO production is regulated at the level or downstream of ETBR activation. In split-open CDs from HS mice, patch clamp analysis revealed significantly higher ENaC activity after MS-275 pretreatment, which was abrogated by an exogenous NO donor. Moreover, flow-induced increases in mIMCD-3 cell NO production were blunted by HDAC1 or calcium inhibition. Taken together, these findings indicate that HS intake induces HDAC1-dependent activation of the ETBR/NO pathway contributing to the natriuretic response.

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