Changes of Plasma Endothelin and Growth Factor Levels, and of Left Ventricular Mass, After Chronic AT1-Receptor Blockade in Human Hypertension

Cottone, Santina; Vadalà, Anna; Vella, M.C.; Nardi, Emilio; Mulè, Giuseppe; Contorno, A; Riccobene, Raffaella; Cerasola, Giovanni

doi:10.1016/s0895-7061(98)00027-2

Cited by 38 publications

(15 citation statements)

References 18 publications

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“…ET-1 is mainly released albuminally from the endothelium towards the underlying smooth muscle, and it is rapidly cleared from the circulation. In arterial hypertension high-to-low circulating values of ET-1 have been reported, 15,29,30 probably due to different methods of assay and different normal range, wideness of the population studied as well as different criteria of enrolment employed. Therefore, it is clear that there are a few difficulties in interpreting the significance of plasma ET-1 concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 Nonetheless, data regarding plasma values of ET-1 in hypertensive subjects with both essential hypertension and renal parenchymal diseases, are still conflicting. [13][14][15] It has also been suggested that a potential increase in the expression of pre-pro-endothelin 1 constitutes one of the mechanisms implicated in TNF␣ glomerular haemodynamic effect. 16 The potential implication of TNF␣ in decreasing glomerular blood flow and filtration rate is explained by alterations in the balance between vasoconstrictive and vasodilating mediators.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of tumour necrosis factor and endothelin-1 between essential and renal hypertensive patients

et al. 1998

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The present study was performed to compare circulating levels of tumour necrosis factor-␣ (TNF␣) and plasma endothelin 1 (ET-1), of hypertensive patients with or without renal failure and with those of normotensive healthy subjects. The study population consisted of 21 healthy normotensive subjects and 22 hypertensive patients, 11 with essential hypertension, and 11 with hypertension and chronic renal failure (CRF).Plasma ET-1 levels, serum TNF␣ and creatinine, creatinine clearance, 24-h urinary albumin excretion (UAE) were assayed, and 24-h blood pressure monitoring was obtained in all subjects. Office blood pressure was similar between hypertensive patients with and without CRF. However, 24-h blood pressure was greater in patients with CRF than in those with essential hypertension and

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of tumour necrosis factor and endothelin-1 between essential and renal hypertensive patients

et al. 1998

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“…The growth-promoting action of Ang II is largely mediated by autocrine and paracrine factors such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF). 62 ACE inhibition abolishes medial smooth muscle PDGF-AB biosynthesis and attenuates cell proliferation in injured carotid arteries. 63 In the rat carotid artery and in certain mesenteric microvessels, the mitogenic effects of Ang II are mediated by bFGF.…”

Section: Dtgr As a Model Of Hypertension And Ang Ii-related Effectsmentioning

confidence: 99%

Hypertension-Induced End-Organ Damage

et al. 1999

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Abstract-Angiotensin (Ang) II-induced organ damage has fascinated students of hypertension since the work of Wilson and Byrom. We are investigating a double transgenic rat (dTGR) model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1) are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, and VEGF expression. The expression of TGF-␤ and deposition of extracellular matrix proteins follows, which is accompanied by fibrinoid vasculitis in small vessels of the heart and kidneys. Angiotensin-converting enzyme inhibitors and AT1 receptor blockers each lowered blood pressure and shifted pressure natriuresis partially leftward by different mechanisms. When combined, they normalized blood pressure, pressure natriuresis, and protected from vasculopathy completely. Renin inhibition lowered blood pressure partially, but protected from vasculopathy completely. Endothelin receptor blockade had no influence on blood pressure but protected from vasculopathy and improved survival. We show evidence that Ang II stimulates oxidative stress directly or indirectly via endothelin 1 and that NFB is upregulated in this model. We speculate that the transcription factors NFB and AP-1 are involved with initiating chemokine and cytokine expression, leading to the above cascade. The unique model and our pharmacological probes will enable us to test these hypotheses. Key Words: angiotensin II Ⅲ rats, transgenic Ⅲ renin Ⅲ nuclear factor-B Ⅲ monocyte chemoattractant protein-1 Ⅲ muscle, smooth, vascular Ⅲ endothelium H ypertension injures blood vessels and thereby causes end-organ damage. The mechanisms are complicated and, although studied for decades in experimental animal models, 1 are only currently being elucidated. From the efforts of many investigators, we are now in the position of constructing a chain of events from the endothelium to the underlying matrix, to the vascular smooth muscle cells, and beyond to the adventitia, and surrounding tissues. The endothelial layer acts as a signal transduction interface for hemodynamic forces in the regulation of vascular tone and chronic structural remodeling of arteries. 2 Effects of mechanical forces on signal transduction and gene expression in endothelial cells have been demonstrated. 3 Mechanical stress initiates numerous pathways including ion channels, integrin interaction between cells and matrix, activation of various tyrosine kinases, autocrine production, and release of growth factors. 4 Increased flow through small arteries has been shown to increase connective tissue production and promote medial hypertrophy, probably through proliferation of both endothelial and vasc...

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“…23 In patients with hypertension or heart failure, chronic blockade of AT 1 resulted in a significant decrease in the circulating levels of TNF-␣. 24,25 More importantly, blockade of TNF-␣ by etanercept has been shown to prevent renal damage in genetically hypertensive rats and to lower blood pressure in rats with hypertension induced by Ang II and salt, suggesting a role for TNF-␣ in blood pressure regulation and renal injury. 26,27 A recent study showed that mice treated with etanercept prevented the hypertension and blunted the increase in superoxide production in response to Ang II.…”

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confidence: 99%

Involvement of Tumor Necrosis Factor-α in Angiotensin II–Mediated Effects on Salt Appetite, Hypertension, and Cardiac Hypertrophy

Sriramula

Haque²,

Majid³

et al. 2008

Hypertension

257

201

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Abstract-Hypertension is considered a low-grade inflammatory condition induced by various proinflammatory cytokines, including tumor necrosis factor (TNF)-␣. Recent studies have implicated an involvement of TNF-␣ in the development of salt-sensitive hypertension induced by angiotensin II (Ang II). To understand further the relationship between TNF-␣ and Ang II, we examined the responses to Ang II in TNF-␣ knockout (TNF-␣ Ϫ/Ϫ ) mice in the present study. A continuous infusion of Ang II (1 g/kg per minute) for 2 weeks was given to both TNF-␣ Ϫ/Ϫ and wild-type (WT) mice with implanted osmotic minipumps. Daily measurement of water intake, salt intake, and urine output were performed using metabolic cages. Blood pressure was monitored continuously with implanted radiotelemetry. Ang II administration for 2 weeks caused increases in salt (0.2Ϯ0.07 to 5.6Ϯ0.95 mL/d) and water (5.4Ϯ0.34 to 11.5Ϯ1.2 mL/d) intake and in mean arterial pressure (115Ϯ1 to 151Ϯ3 mm Hg) in wild-type mice, but these responses were absent in TNF-␣ Ϫ/Ϫ mice (0.2Ϯ0.04 to 0.3Ϯ0.09 mL/d, 5.5Ϯ0.2 to 6.1Ϯ0.07 mL/d, and 113Ϯ2 to 123Ϯ3 mm Hg, respectively). Cardiac hypertrophy induced by Ang II was significantly attenuated in TNF-␣ Ϫ/Ϫ mice compared with wild-type mice. In a group of TNF-␣ Ϫ/Ϫ mice, when replacement therapy was made with recombinant TNF-␣, Ang II induced similar responses in salt appetite, mean arterial pressure, and cardiac hypertrophy, as observed in wild-type mice. These results suggest that TNF-␣ plays a mechanistic role in mediating chronic Ang II-induced effects on salt appetite and blood pressure, as well as on cardiac hypertrophy.

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Changes of Plasma Endothelin and Growth Factor Levels, and of Left Ventricular Mass, After Chronic AT1-Receptor Blockade in Human Hypertension

Cited by 38 publications

References 18 publications

Comparison of tumour necrosis factor and endothelin-1 between essential and renal hypertensive patients

Comparison of tumour necrosis factor and endothelin-1 between essential and renal hypertensive patients

Hypertension-Induced End-Organ Damage

Involvement of Tumor Necrosis Factor-α in Angiotensin II–Mediated Effects on Salt Appetite, Hypertension, and Cardiac Hypertrophy

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