scholarly journals High aminopeptidase A activity contributes to blood pressure control in ob/ob mice by AT2 receptor-dependent mechanism

2017 ◽  
Vol 312 (3) ◽  
pp. H437-H445 ◽  
Author(s):  
Rafael L. Morais ◽  
Aline M. Hilzendeger ◽  
Bruna Visniauskas ◽  
Mihail Todiras ◽  
Natalia Alenina ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Pressure Control ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Angiotensin Iii ◽  
Metabolic Conditions ◽  
Aminopeptidase A

Obesity is assumed to be a major cause of human essential hypertension; however, the mechanisms responsible for weight-related increase in blood pressure (BP) are not fully understood. The prevalence of hypertension induced by obesity has grown over the years, and the role of the renin-angiotensin-aldosterone system (RAAS) in this process continues to be elucidated. In this scenario, the ob/ob mice are a genetic obesity model generally used for metabolic disorder studies. These mice are normotensive even though they present several metabolic conditions that predispose them to hypertension. Although the normotensive trait in these mice is associated with the poor activation of sympathetic nervous system by the lack of leptin, we demonstrated that ob/ob mice present massively increased aminopeptidase A (APA) activity in the circulation. APA enzyme metabolizes angiotensin (ANG) II into ANG III, a peptide associated with intrarenal angiotensin type 2 (AT2) receptor activation and induction of natriuresis. In these mice, we found increased ANG-III levels in the circulation, high AT2 receptor expression in the kidney, and enhanced natriuresis. AT2 receptor blocking and APA inhibition increased BP, suggesting the ANG III-AT2 receptor axis as a complementary BP control mechanism. Circulating APA activity was significantly reduced by weight loss independently of leptin, indicating the role of fat tissue in APA production. Therefore, in this study we provide new data supporting the role of APA in BP control in ob/ob mouse strain. These findings improve our comprehension about obesity-related hypertension and suggest new tools for its treatment. NEW & NOTEWORTHY In this study, we reported an increased angiotensin III generation in the circulation of ob/ob mice caused by a high aminopeptidase A activity. These findings are associated with an increased natriuresis found in these mice and support the role of renin-angiotensin-aldosterone system as additional mechanism regulating blood pressure in this genetic obese strain.

scholarly journals Endothelin, sex, and pregnancy: unique considerations for blood pressure control in females

2016 ◽  
Vol 310 (8) ◽  
pp. R691-R696 ◽  
Author(s):  
Ellen E. Gillis ◽  
Jennifer M. Sasser ◽  
Jennifer C. Sullivan
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Blood Pressure Control ◽  
Pressure Control ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Young Females ◽  
Potential Benefits ◽  
Important Pathway ◽  
Potent Vasoconstrictor

Endothelin-1 (ET-1) is a potent vasoconstrictor, and dysregulation of the endothelin (ET) system has been implicated in the development of hypertension. Sex differences in the ET system have been identified in ET receptor expression and activation, levels of ET-1, and downstream mediators of the ET system. More specifically, males have greater ET-1/ETA receptor activation, whereas females exhibit greater ETB receptor activation. These differences have been suggested to contribute to the sex differences observed in blood pressure control, with greater ETB receptor activation in females potentially acting as an important pathway contributing to the lower prevalence of hypertension in young females compared with age-matched males. This hypothesis is further supported by studies in pregnancy; the role of the ET system is enhanced during pregnancy, with dysregulation of the ET system resulting in preeclampsia. Further research is necessary to elucidate the relative roles of the ET system in blood pressure control in both sexes and to further explore the potential benefits of pharmacological ET blockade in women.

Acromegaly and hypertension: role of the renin-angiotensin-aldosterone system

1982 ◽  
Vol 100 (4) ◽  
pp. 581-587 ◽  
Author(s):  
Bengt E. Karlberg ◽  
Anna-Maria Ottosson
Keyword(s):  
Blood Pressure ◽  
High Frequency ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Substantial Part ◽  
Volume Factor ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Before And After

Abstract. The incidence of arterial hypertension was evaluated in a partly retrospective study of patients with active acromegaly. Of 37 patients studied, 18 (48%) had hypertension, i.e. a supine blood pressure of > 160/95 mmHg. The type of hypertension was explored further by measuring plasma renin activity and, in some patients plasma aldosterone concentrations before and after stimulation (upright posture or furosemide 80 mg given orally). Urinary 24 h excretion of aldosterone was also determined. About half of the patients with hypertension but also a substantial part of normotensive acromegalics had inappropriately low plasma renin levels both during basal conditions and after stimulation. On the other hand urinary aldosterone excretion was either normal or (in 2 patients) slightly elevated. There was no other evidence of coexistent primary aldosteronism. Our results confirm previous reports of a high frequency of alterations in the renin-angiotensin-aldosterone system in acromegalic patients with growth hormone excess which in some instances may lead to an elevated blood pressure. The biochemical changes have many similarities to low renin essential hypertension. A volume factor may be operating in acromegalic patients with hypertension since in 10 patients treatment with the aldosterone antagonist, spironolactone, with doses between 50–200 mg daily lowered blood pressure to near normal levels. Thus, spironolactone seems to be a worthwhile alternative in the treatment of hypertensive acromegalics.

scholarly journals Relationship between the expression of angiotensin II receptors type 1 and vasoactive regulators in arterial hypertension

2020 ◽  
Vol 11 (3) ◽  
pp. 16-21
Author(s):  
Anna V. Logatkina ◽  
Viktor S. Nikiforov ◽  
Stanislav S. Bondar' ◽  
Igor' V. Terekhov ◽  
Vladimir K. Parfeniuk
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Ace Inhibitor ◽  
High Expression ◽  
Soluble Form ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Low Expression

In the pathogenesis of arterial hypertension (AH), the renin-angiotensin-aldosterone system plays a key role in helping to maintain elevated blood pressure. At the same time, the state of angiotensin-II production (AT II) and the expression level of its receptors on target cells determine the formation of most of the effects underlying the pathogenesis of associated clinical conditions in such patients. Thus, the study of the pathogenesis of AH, namely the study of the role of the AT II axis, the AT II receptor, is an actual scientific and practical task. Aim. Given the important role of type 1 receptors for AT II in the formation of pathological changes in arterial hypertension, the purpose of this study was to study the peculiarities of the effect of their expression on biochemical processes in patients with arterial hypertension. Material and methods. In the course of the clinical study, 60 patients of both sexes with hypertension aged 45 to 55 years old were admitted to the clinic for planned treatment. Depending on the initial level of expression of receptors for AT II (AT1R), determined by the serum concentration of the soluble form of type 1 receptors for AT II, the patients were divided into two subgroups with conditionally low (corresponding to the concentration of the soluble form of the receptor for AT II 0.66 ng/ml) and conditionally high (1.57 ng/ml) expression. The analysis showed that high expression of AT1R is associated with elevated plasma levels of renin by 30.8% (p=0.0005), AT II by 48.1% (p=0.00001), E-selectin by 47.9% (p=0.0001), VCAM-1 by 29.1% (p=0.00001), ICAM-1 by 52.9% (p=0.00001), VE-cadherin by 50.9% (p=0.00001), endothelin-1 by 48.8% (p=0.0005), an ACE inhibitor by 13.6% (p=0.047), and CRP by 74.1% (p=0.00002 ) and endoperoxide by 29.7% (p=0.009). Against this background, there was a decrease in the level of apoA1 by 21.6% (p=0.027), ACE by 20.1% (p=0.1), the level of antioxidants by 22.3% (p=0.00001). The analysis showed that in the group with initially high expression of AT1R, there was an increased blood pressure, the level of which, on average, exceeded the values of patients with low expression of the indicated receptor by 24.5 mm Hg (p=0.011). Against the background of therapy in the group with high expression of AT1R, plasma renin activity decreased by 20.3% (p=0.013), endoperoxide by 8.4% (p=0.038), an ACE inhibitor by 14.6% (p=0.02). At the same time, the level of apoA1 increased by 8.5% (p=0.036), antioxidants by 8.6% (p=0.036), ICAM-1 by 5.3% (p=0.05), VE-cadherin by 2.5% (p=0.07). The level of the remaining factors was not statistically significant. In the subgroup with low expression of the AT II receptor, during treatment, there was a decrease in endoperoxide by 12.8% (p=0.031), an ACE inhibitor by 5.5% (p=0.044) without significant changes in other indicators. Conclusion. In hypertensive patients, higher expression of AT1R is associated with high activation of immune-inflammatory mechanisms, dyslipidemia, an imbalance of the lipid peroxidation system and antioxidant protection, as well as higher renin-angiotensin-aldosterone system activity and increased arterial pressure. On the background of antihypertensive therapy, partial compensation of the identified changes is achieved, including a moderate increase in the level of antioxidants, a decrease in the concentration of endoperoxide, renin activity and an increase in the level of apoA1, while maintaining an increased level of AT II, high expression of receptors to it. These changes indicate the need for further search for effective antihypertensive therapy strategies aimed at limiting the activity of renin-angiotensin-aldosterone system in patients with hypertension.

scholarly journals Role of the Renin-Angiotensin-Aldosterone System in Various Disease Processes: An Overview

2021 ◽  
Author(s):  
Volkan Gelen ◽  
Abdulsamed Kükürt ◽  
Emin Şengül
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Electrolyte Balance ◽  
Physiological System ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Working Principle ◽  
Kidney Liver ◽  
Regulation Of Blood Pressure

The renin-angiotensin-aldosterone system is a physiological system that plays an important role in the regulation of blood pressure and body water-electrolyte balance, in which the kidney, liver and lungs play a role in its activation. This system comes into play in various diseases such as the cardiovascular, renal, pulmonary and nervous system where blood pressure and fluid-electrolyte balance may change. The purpose of this study, which is presented in line with this information, is to explain the working principle of this system, how this system is activated, how it comes into play in the mentioned diseases, and what kind of results occur.

Reversal of renovascular hypertension: role of the renal medulla

1987 ◽  
Vol 65 (8) ◽  
pp. 1566-1571 ◽  
Author(s):  
J. D. Swales ◽  
R. F. Bing ◽  
M. E. Edmunds ◽  
G. I. Russell ◽  
H. Thurston
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Peripheral Resistance ◽  
Renin Angiotensin System ◽  
Renal Medulla ◽  
Pressure Control ◽  
Sodium Retention ◽  
Angiotensin System ◽  
Renin Angiotensin

The fall in blood pressure, which occurs when renovascular hypertension is corrected surgically, offers a means of elucidating the factors responsible for blood pressure control. When Goldblatt two-kidney, one-clip hypertension in the rat is reversed by unclipping the renal artery, or by removal of the ischaemic kidney, restoration of normal blood pressure is due to a fall in peripheral resistance. This is associated with sodium retention and cannot be modified by inhibition of the renin–angiotensin system. The fall is, however, partially inhibited by chemical removal of the renal medulla by means of 2-bromo-ethylamine hydrobromide. When normal rats are chemically medullectomized, moderate hypertension is produced, which cannot be attributed to the renin–angiotensin system or sodium retention. It is concluded that a renomedullary vasodepressor system is ablated by chemical medullectomy: further, this system plays a role in the surgical correction of Goldblatt hypertension.

scholarly journals Relationship between the renin–angiotensin–aldosterone system and renal Kir5.1 channels

2019 ◽  
Vol 133 (24) ◽  
pp. 2449-2461 ◽  
Author(s):  
Anna D. Manis ◽  
Oleg Palygin ◽  
Sherif Khedr ◽  
Vladislav Levchenko ◽  
Matthew R. Hodges ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Pressure Control ◽  
Dietary Sodium ◽  
Distal Nephron ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Kir Channel ◽  
And Function ◽  
The Impact

Abstract Kir5.1 (encoded by the Kcnj16 gene) is an inwardly rectifying K+ (Kir) channel highly expressed in the aldosterone-sensitive distal nephron of the kidney, where it forms a functional channel with Kir4.1. Kir4.1/Kir5.1 channels are responsible for setting the transepithelial voltage in the distal nephron and collecting ducts and are thereby major determinants of fluid and electrolyte distribution. These channels contribute to renal blood pressure control and have been implicated in salt-sensitive hypertension. However, mechanisms pertaining to the impact of K ir4.1/Kir5.1-mediated K+ transport on the renin–angiotensin–aldosterone system (RAAS) remain unclear. Herein, we utilized a knockout of Kcnj16 in the Dahl salt-sensitive rat (SSKcnj16-/-) to investigate the relationship between Kir5.1 and RAAS balance and function in the sensitivity of blood pressure to the dietary Na+/K+ ratio. The knockout of Kcnj16 caused substantial elevations in plasma RAAS hormones (aldosterone and angiotensin peptides) and altered the RAAS response to changing the dietary Na+/K+ ratio. Blocking aldosterone with spironolactone caused rapid mortality in SSKcnj16-/- rats. Supplementation of the diet with high K+ was protective against mortality resulting from aldosterone-mediated mechanisms. Captopril and losartan treatment had no effect on the survival of SSKcnj16-/- rats. However, neither of these drugs prevented mortality of SSKcnj16-/- rats when switched to high Na+ diet. These studies revealed that the knockout of Kcnj16 markedly altered RAAS regulation and function, suggesting Kir5.1 as a key regulator of the RAAS, particularly when exposed to changes in dietary sodium and potassium content.

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