Selective Potentiation of Angiotensin-Induced Constriction of Skeletal Muscle Resistance Arteries by Chronic Elevations in Dietary Salt Intake

Weber, David S.; Frisbee, Jefferson C.; Lombard, Julian H.

doi:10.1006/mvre.1999.2147

Cited by 21 publications

(29 citation statements)

References 20 publications

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“…Dysregulation of AngII activity is a possible link between HS intake and development of vascular dysfunction and insulin resistance [6,9,42,43]. Insulin stimulates microvascular recruitment by a process that is at least partly NO-dependent [16,19].…”

Section: Discussionmentioning

confidence: 99%

“…Elevated BP responses to HS intake appear to be heterogeneous in nature [1,2,5,6] with certain animal models and indeed humans displaying insulin resistance in the absence of hypertension [1,2]. Thus, the mechanisms by which elevated sodium intake causes insulin resistance appear to have origins that are separate from or may precede those that cause hypertension.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies highlight structural and functional vascular alterations following HS intake [5,6,9,10,24,25]. These studies provide an important link between vascular dysfunction and hypertension during HS intake.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the primary aim of the current study was to determine whether or not HS-induced insulin resistance develops as a consequence of impaired vascular function in skeletal muscle. Since sodium-induced vascular dysfunction is likely to involve deleterious angiotensin II (AngII) activity [6,9], a secondary aim of the present study was to investigate whether or not the development of sodium-induced insulin resistance can be prevented using the ACE inhibitor quinapril.…”

Section: Introductionmentioning

confidence: 99%

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A vascular mechanism for high-sodium-induced insulin resistance in rats

et al. 2014

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Aims/hypothesis High sodium (HS) effects on hypertension are well established. Recent evidence implicates a relationship between HS intake and insulin resistance, even in the absence of hypertension. The aim of the current study was to determine whether loss of the vascular actions of insulin may be the driving factor linking HS intake to insulin resistance. Methods Sprague Dawley rats were fed a control (0.31% wt/wt NaCl) or HS (8.00% wt/wt NaCl) diet for 4 weeks and subjected to euglycaemic-hyperinsulinaemic clamp (10 mU min) or constant-flow pump-perfused hindlimb studies following an overnight fast. A separate group of HS rats was given quinapril during the dietary intervention and subjected to euglycaemichyperinsulinaemic clamp as above. Results HS intake had no effect on body weight or fat mass or on fasting glucose, insulin, endothelin-1 or NEFA concentrations. However, HS impaired whole body and skeletal muscle glucose uptake, in addition to a loss of insulin-stimulated microvascular recruitment. These effects were present despite enhanced insulin signalling (Akt) in both liver and skeletal muscle. Constant-flow pump-perfused hindlimb experiments revealed normal insulin-stimulated myocyte glucose uptake in HS-fed rats. Quinapril treatment restored insulin-mediated microvascular recruitment and muscle glucose uptake in vivo.Conclusions/interpretation HS-induced insulin resistance is driven by impaired microvascular responsiveness to insulin, and is not due to metabolic or signalling defects within myocytes or liver. These results imply that reducing sodium intake may be important not only for management of hypertension but also for insulin resistance, and highlight the vasculature as a potential therapeutic target in the prevention of insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A vascular mechanism for high-sodium-induced insulin resistance in rats

et al. 2014

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“…9 MT is also influenced by neurohormonal mechanisms via activation of signal transduction pathways that regulate VSMC contraction and growth. 5,10,11 For example, low concentrations of Ang II potentiate MT, whereas higher Ang II concentrations induce contraction of resistance arteries. 12,13 These contractile effects of Ang II are attributed largely to angiotensin II type I receptor (AT 1 -R) activation.…”

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confidence: 99%

Involvement of Metalloproteinases 2/9 in Epidermal Growth Factor Receptor Transactivation in Pressure-Induced Myogenic Tone in Mouse Mesenteric Resistance Arteries

et al. 2004

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Background-Epidermal growth factor receptor (EGFR) transactivation is a mediator of angiotensin II (Ang II) signaling in cultured vascular smooth muscle cells isolated from large arteries. The present study used mouse mesenteric resistance arteries (MRAs) to investigate the role of EGFR transactivation under pressure-induced myogenic tone (MT). Methods and Results-Isolated MRAs were mounted in an arteriograph and stimulated by 25 to 125 mm Hg or with Ang II and KCl. Stepwise increases in pressure resulted in MT development associated with increased EGFR phosphorylation and release of heparin-binding EGF (HB-EGF), a membrane-bound growth factor that is shed on cleavage by metalloproteinases. EGF (50 ng/mL) potentiated MT (59Ϯ1% to 51Ϯ0.6% of passive diameter at 75 mm Hg). Pretreatment with the EGFR inhibitors AG1478 (5 mol/L) or PD153035 (1 mol/L) significantly decreased MT. However, EGFR inhibitors had no effect on Ang II-and KCl-induced contraction. MT was potentiated by HB-EGF, 50 ng/mL, which is bound to the cell membrane and released on cleavage by metalloproteinases. Neutralizing HB-EGF antibodies or heparin treatment to sequester HB-EGF resulted in significant inhibition of pressure-induced MT. MT increased matrix metalloproteinase (MMP) 2 and MMP-9 gelatinase activity assessed by zymography, and specific MMP 2/9 inhibitors significantly decreased MT. Conclusions-These novel findings suggest that the mechanism of pressure-induced MT involves metalloproteinases 2/9 activation with subsequent HB-EGF release and EGFR transactivation.

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Salt, Angiotensin II, Superoxide, and Endothelial Function

Boegehold¹,

Drenjančević-Perić²,

Lombard³

2015

Comprehensive Physiology

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Proper function of the vascular endothelium is essential for cardiovascular health, in large part due to its antiproliferative, antihypertrophic, and anti-inflammatory properties. Crucial to the protective role of the endothelium is the production and liberation of nitric oxide (NO), which not only acts as a potent vasodilator, but also reduces levels of reactive oxygen species, including superoxide anion (O2•-). Superoxide anion is highly injurious to the vasculature because it not only scavenges NO molecules, but has other damaging effects, including direct oxidative disruption of normal signaling mechanisms in the endothelium and vascular smooth muscle cells. The renin-angiotensin system plays a crucial role in the maintenance of normal blood pressure. This function is mediated via the peptide hormone angiotensin II (ANG II), which maintains normal blood volume by regulating Na+ excretion. However, elevation of ANG II above normal levels increases O2•- production, promotes oxidative stress and endothelial dysfunction, and plays a major role in multiple disease conditions. Elevated dietary salt intake also leads to oxidant stress and endothelial dysfunction, but these occur in the face of salt-induced ANG II suppression and reduced levels of circulating ANG II. While the effects of abnormally high levels of ANG II have been extensively studied, far less is known regarding the mechanisms of oxidant stress and endothelial dysfunction occurring in response to chronic exposure to abnormally low levels of ANG II. The current article focuses on the mechanisms and consequences of this less well understood relationship among salt, superoxide, and endothelial function.

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Selective Potentiation of Angiotensin-Induced Constriction of Skeletal Muscle Resistance Arteries by Chronic Elevations in Dietary Salt Intake

Cited by 21 publications

References 20 publications

A vascular mechanism for high-sodium-induced insulin resistance in rats

A vascular mechanism for high-sodium-induced insulin resistance in rats

Involvement of Metalloproteinases 2/9 in Epidermal Growth Factor Receptor Transactivation in Pressure-Induced Myogenic Tone in Mouse Mesenteric Resistance Arteries

Salt, Angiotensin II, Superoxide, and Endothelial Function

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