Enhancement of Glucocorticoid and Mineralocorticoid Receptor Density in the Microcirculation of the Spontaneously Hypertensive Rat

DeLano, Frank A.; Schmid‐Schönbein, Geert W.

doi:10.1080/10739680490266207

Cited by 44 publications

(28 citation statements)

References 62 publications

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“…25 What mechanism may raise the count of circulating leukocytes with pseudopods in the SHR? Although there is no significant difference in circulating levels of corticosteroids between WKY and SHR, 26 glucocorticoid receptors have higher density 27 and sensitivity in SHR than WKY, 28 suggesting that the abnormal response to glucocorticoids is a requirement for sustained elevation of blood pressure in SHR. Fluid shear stress serves to inactivate leukocytes by downregulation of membrane CD18 molecules 29 and retraction of pseudopods.…”

Section: Discussionmentioning

confidence: 98%

Contribution of Fluid Shear Response in Leukocytes to Hemodynamic Resistance in the Spontaneously Hypertensive Rat

Fukuda

Yasu

Kobayashi

et al. 2004

Circulation Research

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Abstract-The mechanisms for elevation of peripheral vascular resistance in spontaneously hypertensive rats (SHR), a glucocorticoid-dependent form of hypertension, are unresolved. An increase in hemodynamic resistance caused by circulating blood may be a factor. Physiological fluid shear stress induces a variety of responses in circulating leukocytes, including pseudopod retraction. Due to high rigidity, leukocytes with pseudopods have greater difficulty to pass through capillaries. Because SHR have more circulating leukocytes with pseudopods, we hypothesize that inhibition of the leukocyte shear response by glucocorticoids in SHR impairs normal leukocyte passage through capillaries and causes enhanced resistance in capillary channels. Fluid shear leads to retraction of pseudopods in normal leukocytes, whereas shear induces pseudopod projection in SHR and dexamethasone-treated Wistar rats.

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Section: Discussionmentioning

confidence: 98%

Contribution of Fluid Shear Response in Leukocytes to Hemodynamic Resistance in the Spontaneously Hypertensive Rat

Fukuda

Yasu

Kobayashi

et al. 2004

Circulation Research

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“…In microvessels, both the GC and the mineralocorticoid receptors are expressed in all layers, and their abundances are greater in spontaneously hypertensive rats than in normotensive controls. 40 Undernutrition could reduce expression of placental 11b-HSD-2 and thereby increase transfer of active GC into the fetal compartment, which in turn could directly bind to vascular GC receptors and inhibit VEGF and VEGF receptor expression and ultimately angiogenesis. Correspondingly, numerous studies have demonstrated an inhibitory effect of GC on VEGF abundance and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Excess Maternal Glucocorticoids in Response to In Utero Undernutrition Inhibit Offspring Angiogenesis

et al. 2014

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To test the hypothesis that inhibition of offspring angiogenesis by maternal undernutrition (MUN) is mediated by maternal glucocorticoids, 3 groups of dams were studied: controls received ad libitum food; MUN dams were food restricted by 50% from day 10 of gestation; and metyrapone (MET) dams were food restricted and treated with 0.5 mg/mL of MET, a glucocorticoid synthesis inhibitor. The MUN reduced birth weights, reduced vascular endothelial growth factor (VEGF) abundance in P1 aortas, reduced VEGF and VEGF-R2 abundances in P1 mesenteric arterioles, reduced arteriolar endothelial nitric oxide synthase abundance, reduced microvessel density in the anterior tibialis, reduced endothelial cell branching in culture, reduced arteriolar immunoreactivity for proliferating cell nuclear antigen (PCNA), increased active caspase 3 in P1 mesenteric arterioles, and decreased matrix metalloproteinase (MMP)-2 and MMP-9 abundances in lysates of P1 aortas. All of these effects were prevented by treatment with metyrapone. Collectively, these findings suggest that reduced angiogenesis in MUN offspring involves direct inhibitory effects of maternal glucorticoid on fetal VEGF and its receptors.

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“…Both endothelial and VSMC MR are involved in BP (in basal conditions and in response to AngII infusion) [11,15,19] in the absence of alteration of renal Na + homeostasis, pointing on a specific role of MR expressed in the vasculature. Indeed, MR expression can be increased in vessels in some pathological situations such as hypertension [5].…”

Section: Discussionmentioning

confidence: 99%

Role of smooth muscle cell mineralocorticoid receptor in vascular tone

Tarjus

Belozertseva

Louis

et al. 2014

Pflugers Arch - Eur J Physiol

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Identification of the mineralocorticoid receptor (MR) in the vasculature (i.e., endothelial and smooth muscle cells) raised the question of its role in vascular function and blood pressure control. Using a mouse model with conditional inactivation of MR in vascular smooth muscle cell (VSMC) (MR(SMKO)), we have recently shown that the VSMC MR is crucial for aldosterone-salt-induced carotid stiffening. In the present study, we have investigated the specific contribution of the VSMC MR in the regulation of vascular tone in large vessels. In MR(SMKO) mice, contractions induced by potassium chloride and calcium (Ca(2+)) are decreased in the aorta, whereas contraction is normal in response to phenylephrine and caffeine. The difference in response to Ca(2+) suggests that the VSMC-specific deficiency of the MR modifies VSM Ca(2+) signaling but without altering the intracellular Ca(2+) store handling. The relaxation induced by acetylcholine is not affected by the absence of MR. However, the relaxation induced by Ach in the presence of indomethacin and the relaxation induced by sodium nitroprussiate are significantly reduced in MR(SMKO) mice compared to controls. Since endothelial nitric oxide synthase (eNOS) activity is increased in mutant mice, their altered relaxation reflects impairment of the nitric oxide (NO) signaling pathway. In addition to altered NO and Ca(2+) signaling, the activity of myosin light chain and its regulators, myosin light chain kinase (MLCK) and myosin phosphatase (MLCP), is reduced. In conclusion, MR expressed in VSMC is required for NO and Ca(2+) signaling pathways and contractile protein activity leading to an altered contraction/relaxation coupling.

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Enhancement of Glucocorticoid and Mineralocorticoid Receptor Density in the Microcirculation of the Spontaneously Hypertensive Rat

Abstract: These results suggest that the enhanced sensitivity of the SHR to glucocorticoids and aldosterone may be in part associated with enhanced glucocorticoid and mineralocorticoid receptor densities in the microcirculation.

Cited by 44 publications

References 62 publications

Contribution of Fluid Shear Response in Leukocytes to Hemodynamic Resistance in the Spontaneously Hypertensive Rat

Contribution of Fluid Shear Response in Leukocytes to Hemodynamic Resistance in the Spontaneously Hypertensive Rat

Excess Maternal Glucocorticoids in Response to In Utero Undernutrition Inhibit Offspring Angiogenesis

Role of smooth muscle cell mineralocorticoid receptor in vascular tone

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