NMDA Receptor Plasticity in the Hypothalamic Paraventricular Nucleus Contributes to the Elevated Blood Pressure Produced by Angiotensin II

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.

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The effects of phentolamine on fructose-fed rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y2012-063 ◽

2012 ◽

Vol 90 (8) ◽

pp. 1075-1085 ◽

Cited By ~ 5

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.

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Elevated blood pressure in spontaneously hypertensive rats consuming a high sucrose diet is associated with elevated angiotensin II and is reversed by vanadium

Journal of Hypertension ◽

10.1097/00004872-199715080-00009 ◽

1997 ◽

Vol 15 (8) ◽

pp. 857-862 ◽

Cited By ~ 17

Author(s):

Shang-Jin Shi ◽

Harry G. Preuss ◽

Darrell R. Abernethy ◽

Xin Li ◽

S Taylor Jarrell ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Spontaneously Hypertensive Rats ◽

Elevated Blood Pressure ◽

Elevated Blood ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose

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Cerebroprotective effects of angiotensin II receptor blockers: candesartan focus

Medical Council ◽

10.21518/2079-701x-2018-16-14-23 ◽

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.

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