Aldosterone and Not Plasminogen Activator Inhibitor-1 Is a Critical Mediator of Early Angiotensin II/
            <i>N</i>
            <sup>G</sup>
            -Nitro-
            <scp>l</scp>
            -Arginine Methyl Ester-Induced Myocardial Injury

Oestreicher, Eveline; Martinez-Vasquez, D.; Stone, James R.; Jónasson, Lárus; Roubsanthisuk, Weranuj; Mukasa, Koji; Adler, Gail K.

doi:10.1161/01.cir.0000097000.51723.6f

Cited by 92 publications

(98 citation statements)

References 39 publications

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“…Our laboratory has previously shown that a chronic HS diet in WT mice or in rats is not associated with cardiac tissue damage (21,26,30,37). We hypothesized that Cav-1 deficiency during the HS diet may affect eNOS expression and/or activity, not only in the blood vessels, but also in the heart.…”

Section: Discussionmentioning

confidence: 95%

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Pojoga

Yao²,

Sinha³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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RA. Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice. Am J Physiol Heart Circ Physiol 294: H1258-H1265, 2008. First published January 4, 2008 doi:10.1152/ajpheart.01014.2007.-Changes in dietary sodium intake are associated with changes in vascular volume and reactivity that may be mediated, in part, by alterations in endothelial nitric oxide synthase (eNOS) activity. Caveolin-1 (Cav-1), a transmembrane anchoring protein in the plasma membrane caveolae, binds eNOS and limits its translocation and activation. To test the hypothesis that endothelial Cav-1 participates in the dietary sodium-mediated effects on vascular function, we assessed vascular responses and nitric oxide (NO)-mediated mechanisms of vascular relaxation in Cav-1 knockout mice (Cav-1 Ϫ/Ϫ ) and wild-type control mice (WT; Cav-1 ϩ/ϩ ) placed on a high-salt (HS; 4% NaCl) or low-salt (LS; 0.08% NaCl) diet for 16 days. After the systolic blood pressure was measured, the thoracic aorta was isolated for measurement of vascular reactivity and NO production, and the heart was used for measurement of eNOS expression and/or activity. The blood pressure was elevated in HS mice treated with N G -nitro-L-arginine methyl ester and more so in Cav-1 Ϫ/Ϫ than WT mice and was significantly reduced during the LS diet. Phenylephrine caused vascular contraction that was significantly reduced in Cav-1 Ϫ/Ϫ (maximum 0.25 Ϯ 0.06 g/mg) compared with WT (0.75 Ϯ 0.22 g/mg) on the HS diet, and the differences were eliminated with the LS diet. Also, vascular contraction in response to membrane depolarization by high KCl (96 mM) was reduced in Cav-1 Ϫ/Ϫ (0.27 Ϯ 0.05 g/mg) compared with WT mice (0.53 Ϯ 0.12 g/mg) on the HS diet, suggesting that the reduced vascular contraction is not limited to a particular receptor. Acetylcholine (10 Ϫ5 M) caused aortic relaxation in WT mice on HS (23.6 Ϯ 3.5%) and LS (23.7 Ϯ 5.5%) that was enhanced in Cav-1 Ϫ/Ϫ HS (72.6 Ϯ 6.1%) and more so in Cav-1 Ϫ/Ϫ LS mice (93.6 Ϯ 3.5%). RT-PCR analysis indicated increased eNOS mRNA expression in the aorta and heart, and Western blots indicated increased total eNOS and phosphorylated eNOS in the heart of Cav-1 Ϫ/Ϫ compared with WT mice on the HS diet, and the genotypic differences were less apparent during the LS diet. Thus Cav-1 deficiency during the HS diet is associated with decreased vasoconstriction, increased vascular relaxation, and increased eNOS expression and activity, and these effects are altered during the LS diet. The data support the hypothesis that endothelial Cav-1, likely through an effect on eNOS activity, plays a prominent role in the regulation of vascular function during substantial changes in dietary sodium intake. endothelium; nitric oxide; vascular smooth muscle; blood pressure; hypertension HIGH-SALT (HS) DIET IS OFTEN associated with increased vascular volume (4, 15). The volume overload triggers suppression of the renin-angiotensin-aldosterone system, leading to increased salt and water excretion and restoration of v...

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Section: Discussionmentioning

confidence: 95%

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Pojoga

Yao²,

Sinha³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Our findings support the studies of others showing that MR mediates vascular inflammation. For example, the MR antagonists decrease oxidative stress and vascular inflammation in animal models (17)(18)(19)(20)(21)44).…”

Section: Discussionmentioning

confidence: 99%

“…Aldosterone infusion induces leukocyte infiltration into arteries of rats and increases the expression of proinflammatory markers (15,16). Mineralocorticoid receptor (MR) antagonists decrease monocyte infiltration into the vascular wall in hypertensive rats, in rats treated with aldosterone, and in hypertensive mice (17)(18)(19)(20)(21). Clinical studies also show that aldosterone increases markers of vascular inflammation.…”

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confidence: 99%

Aldosterone activates endothelial exocytosis

Jeong¹,

Chaupin²,

Matsushita³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Although elevated levels of aldosterone are associated with vascular inflammation, the proinflammatory pathways of aldosterone are not completely defined. We now show that aldosterone triggers endothelial cell exocytosis, the first step in leukocyte trafficking. Exogenous aldosterone stimulates endothelial exocytosis of Weibel-Palade bodies, externalizing P-selectin and releasing von Willebrand factor. Spironolactone, a nonselective mineralocorticoid receptor (MR) blocker, antagonizes aldosterone-induced endothelial exocytosis. Knockdown of the MR also decreases exocytosis, suggesting that the MR mediates exocytosis. Aldosterone triggers exocytosis within minutes, and this effect is not inhibited by actinomycin D, suggesting a nongenomic effect of aldosterone. Aldosterone treatment of endothelial cells increases leukocyte adherence to endothelial cells in culture. Taken together, our data suggest that aldosterone activates vascular inflammation in part through nongenomic, MR-mediated pathways. Aldosterone antagonism may decrease vascular inflammation and cardiac fibrosis in part by blocking endothelial exocytosis.inflammation ͉ mineralocorticoid ͉ P-selectin ͉ vascular ͉ nitric oxide

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“…Systolic BP was assessed by tail-cuff plethysmography on day 6, prior to the animals being killed as previously reported (Martinez et al 2002, Oestreicher et al 2003, Pajoga et al 2010.…”

Section: Bp Measurementsmentioning

confidence: 99%

“…Caveolae and their associated proteins (caveolins) and striatin, a caveolinassociated protein, were recently shown to mediate the non-genomic actions of steroids (Lu et al 2004) and to participate in activation of signaling transduction pathways of membrane receptors, including steroid receptors and type 1 angiotensin II receptor (AT 1 R; Ushio-Fukai et al 2005. We also assessed extracellular signal-regulated kinase (ERK) activity and plasminogen activator inhibitor-1 (PAI-1) as these factors are activated by both ANGII and aldosterone and have adverse effects on the heart (Oestreicher et al 2003). Finally, the effects of sodium intake on cardiac endothelial nitric oxide synthase (eNOS) activity were assessed as NO has beneficial CV effects that could counter the adverse effects of ANGII/ aldosterone.…”

Section: Introductionmentioning

confidence: 99%

Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart

Ricchiuti¹,

Lapointe²,

Pojoga³

et al. 2011

Journal of Endocrinology

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Liberal or high-sodium (HS) intake, in conjunction with an activated renin-angiotensin-aldosterone system, increases cardiovascular (CV) damage. We tested the hypothesis that sodium intake regulates the type 1 angiotensin II receptor (AT 1 R), mineralocorticoid receptor (MR), and associated signaling pathways in heart tissue from healthy rodents. HS (1 . 6% Na C ) and low-sodium (LS; 0 . 02% Na C ) rat chow was fed to male healthy Wistar rats (nZ7 animals per group). Protein levels were assessed by western blot and immunoprecipitation analysis. Fractionation studies showed that MR, AT 1 R, caveolin-3 (CAV-3), and CAV-1 were located in both cytoplasmic and membrane fractions. In healthy rats, consumption of an LS versus a HS diet led to decreased cardiac levels of AT 1 R and MR. Decreased sodium intake was also associated with decreased cardiac levels of CAV-1 and CAV-3, decreased immunoprecipitation of AT 1 R-CAV-3 and MR-CAV-3 complexes, but increased immunoprecipitation of AT 1 R/MR complexes. Furthermore, decreased sodium intake was associated with decreased cardiac extracellular signal-regulated kinase (ERK), phosphorylated ERK (pERK), and pERK/ ERK ratio; increased cardiac striatin; decreased endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS), but increased peNOS/eNOS ratio; and decreased cardiac plasminogen activator inhibitor-1. Dietary sodium restriction has beneficial effects on the cardiac expression of factors associated with CV injury. These changes may play a role in the cardioprotective effects of dietary sodium restriction.

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Aldosterone and Not Plasminogen Activator Inhibitor-1 Is a Critical Mediator of Early Angiotensin II/ N ^G -Nitro- l -Arginine Methyl Ester-Induced Myocardial Injury

Cited by 92 publications

References 39 publications

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Aldosterone activates endothelial exocytosis

Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart

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Aldosterone and Not Plasminogen Activator Inhibitor-1 Is a Critical Mediator of Early Angiotensin II/ N G -Nitro- l -Arginine Methyl Ester-Induced Myocardial Injury

Cited by 92 publications

References 39 publications

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

Aldosterone activates endothelial exocytosis

Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart

Contact Info

Product

Resources

About

Aldosterone and Not Plasminogen Activator Inhibitor-1 Is a Critical Mediator of Early Angiotensin II/ N ^G -Nitro- l -Arginine Methyl Ester-Induced Myocardial Injury