scholarly journals Perinatal α-tocopherol overload programs alterations in kidney development and renal angiotensin II signaling pathways at birth and at juvenile age: Mechanisms underlying the development of elevated blood pressure

2018 ◽  
Vol 1864 (7) ◽  
pp. 2458-2471 ◽  
Author(s):  
Valdilene S. Ribeiro ◽  
Edjair V. Cabral ◽  
Leucio D. Vieira ◽  
Regina S. Aires ◽  
Juliane S. Farias ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Signaling Pathways ◽  
Kidney Development ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Juvenile Age ◽  
Angiotensin Ii Signaling

Angiotensin II promotes aortic valve thickening independent of elevated blood pressure in apolipoprotein-E deficient mice

2013 ◽  
Vol 226 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Tomohiro Fujisaka ◽  
Masaaki Hoshiga ◽  
Junko Hotchi ◽  
Yoshihiro Takeda ◽  
Denan Jin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Aortic Valve ◽  
Apolipoprotein E ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Deficient Mice

scholarly journals Renal Natriuretic Peptide Receptor-C Deficiency Attenuates NaCl Cotransporter Activity in Angiotensin II–Induced Hypertension

Hypertension ◽  
2021 ◽  
Vol 77 (3) ◽  
pp. 868-881
Author(s):  
Shuai Shao ◽  
Xiao-Dong Li ◽  
Yuan-Yuan Lu ◽  
Shi-Jin Li ◽  
Xiao-Hui Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Natriuretic Peptide ◽  
Elevated Blood Pressure ◽  
Natriuretic Peptide Receptor ◽  
Sodium Retention ◽  
Ang Ii ◽  
Elevated Blood ◽  
Peptide Receptor ◽  
Induced Hypertension

Genome-wide association studies have identified that NPR-C (natriuretic peptide receptor-C) variants are associated with elevation of blood pressure. However, the mechanism underlying the relationship between NPR-C and blood pressure regulation remains elusive. Here, we investigate whether NPR-C regulates Ang II (angiotensin II)-induced hypertension through sodium transporters activity. Wild-type mice responded to continuous Ang II infusion with an increased renal NPR-C expression. Global NPR-C deficiency attenuated Ang II–induced increased blood pressure both in male and female mice associated with more diuretic and natriuretic responses to a saline challenge. Interestingly, Ang II increased both total and phosphorylation of NCC (NaCl cotransporter) abundance involving in activation of WNK4 (with-no-lysine kinase 4)/SPAK (Ste20-related proline/alanine-rich kinase) which was blunted by NPR-C deletion. NCC inhibitor, hydrochlorothiazide, failed to induce natriuresis in NPR-C knockout mice. Moreover, low-salt and high-salt diets–induced changes of total and phosphorylation of NCC expression were normalized by NPR-C deletion. Importantly, tubule-specific deletion of NPR-C also attenuated Ang II–induced elevated blood pressure, total and phosphorylation of NCC expression. Mechanistically, in distal convoluted tubule cells, Ang II dose and time-dependently upregulated WNK4/SPAK/NCC kinase pathway and NPR-C/Gi/PLC/PKC signaling pathway mediated NCC activation. These results demonstrate that NPR-C signaling regulates NCC function contributing to sodium retention-mediated elevated blood pressure, which suggests that NPR-C is a promising candidate for the treatment of sodium retention-related hypertension.

scholarly journals The effects of phentolamine on fructose-fed rats

2012 ◽  
Vol 90 (8) ◽  
pp. 1075-1085 ◽  
Author(s):  
Kangbin Zhou ◽  
Ujendra Kumar ◽  
Violet G. Yuen ◽  
John H. McNeill
Keyword(s):  
Blood Pressure ◽  
Uric Acid ◽  
Angiotensin Ii ◽  
Plasma Levels ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Medical Disorders ◽  
Dietary Fructose ◽  
Plasma Nitrate

Metabolic syndrome (MS) is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. MS is associated with obesity, increased blood pressure, hyperlipidemia, and hyperglycemia. This study was designed to investigate the pharmacological profile of phentolamine, a nonselective α adrenergic receptor antagonist, in the prevention of increased blood pressure in fructose-fed rats. Phentolamine prevented the fructose-induced increase in systolic blood pressure without affecting insulin sensitivity and major metabolic parameters. The levels of plasma noradrenaline and angiotensin II, 2 proposed contributors to the development of fructose-induced elevated blood pressure, were examined. Neither noradrenaline nor angiotensin II levels were affected by phentolamine treatment. Since overproduction of nitric oxide has been shown to lead to an elevation in peroxynitrite, the role of oxidative stress, a proposed mechanism of fructose-induced elevated blood pressure and insulin resistance, was examined by measuring plasma levels of total nitrate/nitrite. Plasma nitrate/nitrite was significantly elevated in all fructose-fed animals, regardless of treatment with phentolamine. Another proposed contributor toward fructose-induced MS is an elevation in uric acid levels. In this experiment, plasma levels of uric acid were found to be increased by dietary fructose and were unaffected by phentolamine treatment.

scholarly journals Cerebroprotective effects of angiotensin II receptor blockers: candesartan focus

2018 ◽  
pp. 14-23
Author(s):  
O. D. Ostroumova ◽  
A. I. Kochetkov ◽  
T. M. Ostroumova ◽  
E. E. Pavleeva
Keyword(s):  
Blood Pressure ◽  
Cognitive Impairment ◽  
Angiotensin Ii ◽  
Cognitive Disorders ◽  
Early Morning ◽  
Elevated Blood Pressure ◽  
Angiotensin Ii Receptor Blocker ◽  
Elevated Blood ◽  
Angiotensin Ii Receptor ◽  
Cerebrovascular Complications

The article is devoted to the role of antihypertensive drugs in cerebroprotection, importance of such drugs in reducing the risk of stroke and cognitive disorders in patients with arterial hypertension (AH). The article provides the definition, classification and pathogenetic mechanisms of cognitive impairment in elevated blood pressure (BP). It also presents epidemiological characteristics of the incidence of stroke and cognitive disorders in hypertension. The influence of elevated blood pressure as a factor increasing the risk of cerebrovascular complications is considered. Particular attention is paid to the issue of a sharp rise in BP in the early morning hours, which is typical for patients with AH. The clinical significance of excessive early morning hypertension is discussed. The authors emphasize the difficulties and importance of correcting the morning rises in blood pressure as one of the objectives of antihypertensive therapy. The article presents data on the distinctive features of the pharmacokinetics and pharmacodynamics of candesartan, an angiotensin II receptor blocker with an extremely long-term action. The clinical efficacy of candesartan in the treatment of AH and the risk of cerebrovascular complications, especially stroke and cognitive impairment, has been demonstrated from the point of view of evidence-based medicine.

scholarly journals Transgenic mice expressing an intracellular fluorescent fusion of angiotensin II demonstrate renal thrombotic microangiopathy and elevated blood pressure

2010 ◽  
Vol 298 (6) ◽  
pp. H1807-H1818 ◽  
Author(s):  
K. M. Redding ◽  
B. L. Chen ◽  
A. Singh ◽  
R. N. Re ◽  
L. G. Navar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Transgenic Mice ◽  
Fusion Protein ◽  
Thrombotic Microangiopathy ◽  
Fluorescent Imaging ◽  
Elevated Blood Pressure ◽  
Ang Ii ◽  
Elevated Blood ◽  
Wild Type

We have generated transgenic mice that express angiotensin II (ANG II) fused downstream of enhanced cyan fluorescent protein, expression of which is regulated by the mouse metallothionein promoter. The fusion protein, which lacks a secretory signal, is retained intracellularly. In the present study, RT-PCR, immunoblot analyses, whole-animal fluorescent imaging, and fluorescent microscopy of murine embryonic fibroblasts confirm expression of the fusion protein in vivo and in vitro. The transgene is expressed in all tissues tested (including brain, heart, kidney, liver, lung, and testes), and radioimmunoassay of plasma samples obtained from transgenic mice indicate no increase in circulating ANG II over wild-type levels, consistent with intracellular retention of the transgene product. Kidneys from transgenic and corresponding wild-type littermates were histologically evaluated, and abnormalities in transgenic mice consistent with thrombotic microangiopathy were observed; microthrombosis was frequently observed within the glomerular capillaries and small vessels. In addition, systolic and diastolic blood pressures, measured by telemetry ( n = 8 for each group), were significantly higher in transgenic mice compared with wild-type littermates. Blood pressure of line A male transgenic mice was 125 ± 1.7 over 97 ± 1.6 compared with 109 ± 1.7 over 83 ± 1.4 mmHg in wild-type littermates (systolic over diastolic). In summary, overexpression of an intracellular fluorescent fusion protein of ANG II correlates with elevated blood pressure and kidney pathology. This transgenic model may be useful to further explore the intracellular renin-angiotensin system and its implication in abnormal kidney function and hypertension.

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