Silica attenuates hypertension in Lyon hypertensive rats

Bataillard, Alain; Renaudin, C; Sassard, J

doi:10.1097/00004872-199512010-00012

Cited by 16 publications

(11 citation statements)

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“…5). The decreased blood pressure by PDTC inhibition in this study is also consistent with the fact that suppression of acute inflammation may lower the blood pressure in the Lyon hypertensive model 44. The dose we used in this study (150 mg per day) has been applied in other studies without indication for toxic effect29.…”

Section: Discussionsupporting

confidence: 84%

Nuclear Factor Kappa B and Matrix Metalloproteinase Induced Receptor Cleavage in the Spontaneously Hypertensive Rat

Schmid‐Schönbein

2011

Hypertension

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Abstract-Recent evidence suggests that inflammation in the spontaneously hypertensive rat (SHR) is associated with an uncontrolled matrix metalloproteinase (MMP) activity. We hypothesize that the transcription factor nuclear factor kappa B (NFB) is overexpressed in the SHR, enhancing its MMP activity and enzymatic cleavage of the ␤2 adrenergic receptor (␤ 2 AR), thereby diminishing catecholamine-mediated arteriolar vasodilation. NFB expression level and translocation were compared between Wistar Kyoto rat and SHR kidney, heart, and brain. The animals were treated with NFB inhibitor, pyrrolidine dithiocarbamate, for 10 weeks and correlations between NFB and MMP activity were determined. Immunohistochemistry showed that NFB expression is increased in untreated SHR kidney (Ϸ14%) and brain hypothalamus (Ϸ22%) compared to that in Wistar Kyoto rats (PϽ0.05), but not in myocardium and cerebral cortex. After pyrrolidine dithiocarbamate treatment, the SHR systolic blood pressure was reduced to close to Wistar Kyoto rat levels. NFB expression level in treated SHR was also decreased in kidney and hypothalamus compared to nontreated animals (PϽ0.05). Furthermore, MMP-2 and MMP-9 activities in SHR plasma were significantly reduced (Ϸ41%) by pyrrolidine dithiocarbamate treatment. Additionally, zymographic analyses and in situ zymography showed decreased MMP-2 activity in kidney homogenates and decreased MMP-1 and MMP-9 activities in brain. [1][2][3][4] There is increasing evidence suggesting a strong association between hypertension and inflammation, as well as end-organ damage, 3-7 eg, expression of inducible nitric oxide synthase and inflammatory markers, elevated levels of activated leukocytes in the circulation, enhanced leukocytes cytotoxicity, oxidative stress, and apoptosis. [5][6][7][8][9][10][11][12] We recently obtained evidence that members of the matrix metalloproteinase (MMP) family, 13 known to degrade the extracellular matrix and connective tissue proteins in different physiological and pathological conditions, 14 -16 have elevated levels in hypertension. In the spontaneously hypertensive rat (SHR), elevated levels of MMP-2, MMP-9, and MMP-7 cause direct damage to cells by cleavage of the extracellular domain of several key receptors, which results in diverse cell dysfunctions. 12 For example, proteolytic cleavage of the vasodilatory ␤2 adrenergic receptor (␤ 2 AR) causes arteriolar constriction and blood pressure elevation, 17 cleavage of the extracellular domain of the insulin receptor produces insulin resistance, 18 and cleavage of the vascular endothelial growth factor receptor-2 leads to endothelial cell apoptosis and capillary rarefaction in the SHR. 19 ␤ 2 AR is a cell surface receptor associated with sympathetic nervous system pathways and is involved in mediating smooth muscle vasodilation to balance vascular tone and blood pressure homeostasis. 20,21 Overexpression of the ␤ 2 AR gene in the endothelium of the carotid artery serves to restore vasorelaxation in SHR. 22 Several studies also have shown a...

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Section: Discussionsupporting

confidence: 84%

Nuclear Factor Kappa B and Matrix Metalloproteinase Induced Receptor Cleavage in the Spontaneously Hypertensive Rat

Schmid‐Schönbein

2011

Hypertension

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“…Several studies have recently provided further support to the inflammation/hypertension association by demonstrating higher hsCRP levels among patients with blood pressure in the 'pre-hypertension' stage (that is, systolic blood pressure (BP) 120-139mmHg or diastolic BP 80-89 mm Hg) when compared with normotensive subjects [12,13,50]. In a large cross sectional study, for example, King et al demonstrated that prehypertensive participants (BP [120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139] mm Hg and/or diastolic BP 80-89 mm Hg) had a higher prevalence of elevated hsCRP levels than normotensive subjects (27.4% vs. 19.8%; p<0.05) [13].…”

Section: C-reactive Protein (Crp)mentioning

confidence: 99%

“…There is evidence in both human and animal models linking hypertension to alterations of both humoral and cellular immunity, which might suggest a primary role for inflammation in the causation of hypertension [134][135][136]. For example, the in vivo administration of silica, which is selectively toxic to monocytes, has been shown to reduce the degree of hypertension in Lyon hypertensive rats [137]. However, hypertension itself has been shown to lead to the activation of nuclear transcription factor NF-κB, which induces the transcription of a large range of inflammatory genes, such as those coding IL-6, MCP-1, VCAM-1 and ICAM-1 [138,139].…”

Section: Other Inflammation Sensitive Vascular Markers That Have Founmentioning

confidence: 99%

Is Hypertension an Inflammatory Process?

Boos

Lip²

2006

CPD

142

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The risk factors for hypertension are only partly known, and accounts for the some of the deficiencies in current primary prevention strategies and in the design of new drugs for the management of this common condition. Recently, chronic low grade low-grade inflammation has been identified as an integral part in the pathogenesis of vascular disease. Of note, inflammation may also be implicated in the development of hypertension, either as a primary or secondary event. Indeed, several clinical studies have demonstrated increased numbers of well recognised pro-inflammatory markers, such as high sensitive C-reactive protein (hsCRP), in patients with hypertension, even after adjustment for potential confounding factors. Furthermore, elevated hsCRP levels have also been shown to be predictive for the development of hypertension in prehypertensive and normotensive patients. Pathophysiologically, inflammation has been implicated in both endothelial (dys)function and arterial stiffness in hypertension, with reduced availability of nitric oxide (NO) being integral to this process. Oxidative stress also appears to be a key feature in the reduced availability of NO and is aggravated by increased circulating angiotensin II (Ang II). Importantly, there is some evidence that drugs commonly used in the management of hypertension, such as statins, angiotensin converting enzyme inhibitors and Ang II receptor blockers have anti-inflammatory properties that can positively influence outcomes in patients with hypertension. The inflammatory state in hypertension may pose a new therapeutic target for future drug design.

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“…These rats exhibit spontaneous and agedependent elevation of plasma lipids (Sassolas et al 1981) and development of hypertension involves macrophage activation (Bataillard et al 1995), increased sensitivity to the effects of the renin±angiotensin system (Liu et al 1996) and renal structural alterations (Blanc-Brunat et al 1980). Spontaneously hypertensive rats of the Lyon strain (LH rats) possess several phenotypic traits that may promote development of renal SB + lesions.…”

mentioning

confidence: 99%

Nitric oxide and preglomerular vascular lesions in Lyon spontaneously hypertensive rats

Casellas

Bouriquet

Artuso

2000

Acta Physiologica Scandinavica

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Accumulation of Sudan black-stainable (SB+) lipids is a hallmark of the focal inflammato-proliferative lesions that develop along preglomerular vessels in N G-nitro-L-arginine methyl ester (L-NAME) and angiotensin II hypertensive rats. We extended our findings to genetically hypertensive Lyon (LH) rats aged 14 and 30 weeks and to age-matched normotensive (LN) rats. Vessels were isolated by HCl maceration. Despite high systolic blood pressure (SBP), hypercholesterolaemia, albuminuria and increased interlobular and afferent arteriolar media thickness, SB+ lesions were rarely found in LH rats, regardless of age. To probe nitric oxide as a potential source of vascular protection, 14-week-old LN and LH rats received L-NAME for 10 days (20 mg kg-1 day-1, per os), which increased SBP to 174 +/- 5 and to >200 mmHg, respectively. It induced formation of focal SB+ lesions less frequently in LN than LH rats, in which they affected 39 +/- 7, 44 +/- 5 and 15 +/- 5% of arcuate arterial branches, interlobular arteries and afferent arterioles, respectively. Immunoreactive endothelin-1 was found to accumulate at the level of SB+ lesions. Co-administered with L-NAME, hydralazine (15 mg kg-1 day-1, per os) limited SBP rise to approximately 10 mmHg in both LN and LH rats. As a result, SB+ lesions were rare in LN rats, but were frequent in LH rats. In conclusion, preglomerular SB+ lesions are spontaneously lacking in LH rats. Endogenous nitric oxide production provides protection against vascular barotrauma. Endothelin-1 likely plays an autocrine/paracrine role in vascular lesion formation.

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Silica attenuates hypertension in Lyon hypertensive rats

Cited by 16 publications

References 0 publications

Nuclear Factor Kappa B and Matrix Metalloproteinase Induced Receptor Cleavage in the Spontaneously Hypertensive Rat

Nuclear Factor Kappa B and Matrix Metalloproteinase Induced Receptor Cleavage in the Spontaneously Hypertensive Rat

Is Hypertension an Inflammatory Process?

Nitric oxide and preglomerular vascular lesions in Lyon spontaneously hypertensive rats

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