Effect of increased potassium intake on the renin–angiotensin–aldosterone system and subcutaneous resistance arteries: a randomized crossover study

2020 ◽  
Author(s):  
Rasmus Dreier ◽  
Bahareh Abdolalizadeh ◽  
Camilla L Asferg ◽  
Lisbet R Hölmich ◽  
Niels H Buus ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Crossover Study ◽  
Vascular Function ◽  
Plasma Concentrations ◽  
Resistance Arteries ◽  
Renin Angiotensin Aldosterone System ◽  
Potassium Supplement ◽  
Renin Angiotensin ◽  
Potassium Intake ◽  
Urinary Potassium

Abstract Background Increased potassium intake lowers blood pressure (BP) in hypertensive patients. The underlying mechanism is not fully understood but must be complex because increased potassium intake elevates circulating concentrations of the BP-raising hormone aldosterone. Methods In a randomized placebo-controlled crossover study in 25 normotensive men, we investigated the effect of 4 weeks of potassium supplement (90 mmol/day) compared with 4 weeks of placebo on the renin–angiotensin–aldosterone system (RAAS), urine composition and 24-h ambulatory BP. Vascular function was also assessed through wire myograph experiments on subcutaneous resistance arteries from gluteal fat biopsies. Results Higher potassium intake increased urinary potassium excretion (144.7 ± 28.7 versus 67.5 ± 25.5 mmol/24-h; P < 0.0001) and plasma concentrations of potassium (4.3 ± 0.2 versus 4.0 ± 0.2 mmol/L; P = 0.0002), renin {mean 16 [95% confidence interval (CI) 12–23] versus 11 [5–16] mIU/L; P = 0.0047}, angiotensin II [mean 10.0 (95% CI 6.2–13.0) versus 6.1 (4.0–10.0) pmol/L; P = 0.0025] and aldosterone [mean 440 (95% CI 336–521) versus 237 (173–386) pmol/L; P < 0.0001]. Despite RAAS activation, systolic BP (117.6 ± 5.8 versus 118.2 ± 5.2 mmHg; P = 0.48) and diastolic BP (70.8 ± 6.2 versus 70.8 ± 6.3 mmHg; P = 0.97) were unchanged. In the wire myograph experiments, higher potassium intake did not affect endothelial function as assessed by acetylcholine [logarithmically transformed half maximal effective concentration (pEC50): 7.66 ± 0.95 versus 7.59 ± 0.85; P = 0.86] and substance P (pEC50: 8.42 ± 0.77 versus 8.41 ± 0.89; P = 0.97) or vascular smooth muscle cell reactivity as assessed by angiotensin II (pEC50: 9.01 ± 0.86 versus 9.02 ± 0.59; P = 0.93) and sodium nitroprusside (pEC50: 7.85 ± 1.07 versus 8.25 ± 1.32; P = 0.25) but attenuated the vasodilatory response of retigabine (pEC50: 7.47 ± 1.16 versus 8.14 ± 0.90; P = 0.0084), an activator of Kv7 channels. Conclusions Four weeks of increased potassium intake activates the RAAS in normotensive men without changing BP and this is not explained by improved vasodilatory responses ex vivo.

scholarly journals Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study

2021 ◽  
Author(s):  
Rasmus Dreier ◽  
Ulrik B. Andersen ◽  
Julie L. Forman ◽  
Majid Sheykhzade ◽  
Martin Egfjord ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Crossover Study ◽  
Plasma Concentrations ◽  
Peripheral Resistance ◽  
Cardiovascular Responses ◽  
Mineralocorticoid Receptors ◽  
Aldosterone Secretion ◽  
Potassium Supplement ◽  
Potassium Intake

Background Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure‐raising hormone aldosterone. Besides its well‐described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors‐independent actions are also thought to be involved. Methods and Results To gain further insight into the effect of increased potassium intake and potassium‐stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo‐controlled double‐blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure‐monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; P =0.0002) and aldosterone (median [interquartile range], 440 [336–521] versus 237 [173–386] pmol/L; P <0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII‐stimulated aldosterone secretion ( P =0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo. Conclusions Increased potassium intake potentiates AngII‐stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. Registration EudraCT Number: 2013‐004460‐66; URL: https://www.ClinicalTrials.gov ; Unique identifier: NCT02380157.

Comparative Effects of Atrial Natriuretic Peptide and Brain Natriuretic Peptide on the Aldosterone and Pressor Responses to Angiotensin Ii in Man

1995 ◽  
Vol 88 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Robert I. Cargill ◽  
Allan D. Struthers ◽  
Brian J. Lipworth
Keyword(s):  
Steady State ◽  
Angiotensin Ii ◽  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Concentrations ◽  
Plasma Aldosterone ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Atrial Natriuretic

1. Atrial natriuretic peptide and brain natriuretic peptide have similar vasodilator and natriuretic properties, although little information is available regarding their relative effects as antagonists of the renin—angiotensin—aldosterone system. We have therefore compared how atrial natriuretic peptide and brain natriuretic peptide affect the systemic pressor and aldosterone responses to angiotensin II in eight male subjects. 2. Each subject was studied on three separate occasions, when they received a 60-min infusion of placebo, atrial natriuretic peptide (10 pmol min−1 kg−1) or brain natriuretic peptide (10 pmolmin−1 kg−1), with a concomitant infusion of angiotensin II (6 ng min−1 kg−1) given for the final 30 min of the infusion period. The change in haemodynamic parameters and plasma aldosterone induced by angiotensin II was measured. Plasma concentrations of atrial natriuretic peptide (182 ± 23 pmol/l) and brain natriuretic peptide (193 ± 25 pmol/l) achieved at steady-state during the infusion on each study day were not significantly different. 3. Increases in mean arterial pressure in response to angiotensin II were significantly lowered by concomitant infusion of atrial natriuretic peptide (21.0 ± 1.7 mmHg) and brain natriuretic peptide (20.1 ± 1.9 mmHg) compared with placebo (29.0 ± 4.1 mmHg). There were similar effects on systolic and diastolic blood pressure. Cardiac output was decreased on each study day to the same extent by angiotensin II infusion. Total systemic vascular resistance showed a non-significant trend towards an attenuated response to angiotensin II when atrial natriuretic peptide or brain natriuretic peptide was infused concomitantly in comparison with placebo. 4. Plasma aldosterone increased by 326 ± 49 pmol/l when angiotensin II was infused with placebo. Both atrial natriuretic peptide and brain natriuretic peptide significantly blunted this response, although the increase with atrial natriuretic peptide (19 ± 35 pmol/l) was significantly lower than the increase with brain natriuretic peptide (133 ± 19 pmol/l). 5. Atrial natriuretic peptide and brain natriuretic peptide were therefore equally effective in blunting the systemic pressor response to angiotensin II. It was apparent, however, in view of similar plasma concentrations at steady state, that on a molar basis atrial natriuretic peptide was a more potent inhibitor of angiotensin II-induced aldosterone secretion than brain natriuretic peptide. These results suggest a dissociation between the haemodynamic and hormonal effects of atrial natriuretic peptide and brain natriuretic peptide in terms of antagonism of the renin—angiotensin—aldosterone system.

scholarly journals Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury

2021 ◽  
Author(s):  
Davide Ventura ◽  
Amy L Carr ◽  
R Duane Davis ◽  
Scott Silvestry ◽  
Linda Bogar ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Ii Receptor ◽  
Pulmonary Tissue ◽  
Renin Angiotensin Aldosterone System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Receptor Blockers ◽  
Membrane Bound ◽  
Raas Inhibitors ◽  
Novel Coronavirus

Abstract It has been established SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocytes pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) in the current pandemic. ACE2 serves as regulatory enzyme in maintaining homeostasis between proinflammatory Angiotensin II and anti-inflammatory Angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome (ARDS). Augmentation of the ACE2/Ang1,7 axis represent a critical target in the supportive management of COVID-19 associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

Diurnal change in plasma atrial natriuretic peptide concentrations

1987 ◽  
Vol 73 (5) ◽  
pp. 489-495 ◽  
Author(s):  
A. M. Richards ◽  
G. Tonolo ◽  
R. Fraser ◽  
J. J. Morton ◽  
B. J. Leckie ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Atrial Natriuretic Peptide ◽  
Antidiuretic Hormone ◽  
Natriuretic Peptide ◽  
Plasma Concentrations ◽  
Dietary Sodium ◽  
Sodium Balance ◽  
Diurnal Changes ◽  
Renin Angiotensin ◽  
Atrial Natriuretic

1. Diurnal changes in plasma concentrations of atrial natriuretic peptide (ANP), renin, angiotensin II, aldosterone, Cortisol and antidiuretic hormone were investigated in seven normal volunteers studied under standardized conditions of dietary sodium, posture and physical activity. After completion of the diurnal study serial measurements of these variables were continued during, and on recovery from, a 2 day period of severe sodium depletion. 2. Clear diurnal variations in plasma concentrations of renin, angiotensin II, aldosterone, Cortisol and antidiuretic hormone were observed. 3. Plasma ANP concentrations also varied significantly over 24 h. Values peaked about mid-day and a distinct trough in peptide concentrations occurred in the early evening. However, variations in plasma ANP values were of relatively small amplitude and not clearly independent of modest parallel shifts in sodium balance. 4. Changes in plasma ANP concentrations both within the diurnal study period and during sodium deprivation were closely and positively correlated with concomitant changes in cumulative sodium balance. 5. No simple parallel or reciprocal relationships between plasma concentrations of ANP, on the one hand, and concurrent plasma concentrations of other hormones or in the rate of urinary sodium excretion, on the other, were observed during the 25 h of the diurnal study.

scholarly journals Renin-angiotensin-aldosterone system inhibitors – a realm of confusion in COVID-19

2021 ◽  
Vol 4 (Special2) ◽  
pp. 389-394
Author(s):  
Angela Madalina Lazar
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Current Knowledge ◽  
Angiotensin Receptor Blockers ◽  
Protective Effects ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Raas Inhibitors

Currently, there is a persisting dispute regarding the renin-angiotensin-aldosterone-system (RAAS) inhibitors' safety of use in COVID-19 pandemics. On one side, RAAS inhibitors appear to determine an overexpression of ACE2, the receptor of SARS-CoV-2. Therefore, they could increase the risk of SARS-CoV-2 infection and its degree of severity. On the other side, the discontinuation of RAAS leads to cardiovascular decompensation and has been discouraged by the major medical societies. Also, large-cohort studies report beneficial or at least neutral effects for the RAAS inhibitors in COVID-19 patients. Worldwide, millions of patients receive RAAS inhibitors for the treatment of hypertension and other important comorbidities. In this context, knowledge of the exact effect of these medications becomes of crucial significance. This paper aims to fill in a gap in the current knowledge and presents a putative mechanism by which RAAS inhibitor administration's beneficial results can be explained better. RAAS inhibitors can be beneficial, as they counteract the excessive detrimental activation of the classical angiotensin-converting enzyme (ACE) axis, decreasing the angiotensin II levels. The angiotensin receptor blockers (ARBs) increase the angiotensin II levels, while the angiotensin-converting enzyme inhibitors (ACEI) increase the angiotensin I levels; these substrates will compete with the SARS-CoV-2 for the ACE2 binding, decreasing the viral infectivity. In addition, following the RAAS inhibitors treatment, the up-regulated ACE2 will cleave these substrates (angiotensin I and II), particularly to angiotensin 1-7 that possesses vasodilator, protective effects.

scholarly journals Aliskiren, Fosinopril, and Their Outcome on Renin-Angiotensin-Aldosterone System (RAAS) in Rats with Thyroid Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Susan A. S. Farhadi ◽  
Kawa F. Dizaye
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Positive Control ◽  
Urine Flow ◽  
Angiotensin I ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Group 6 ◽  
Renin Level ◽  
Excretion Rates

Background and Objectives. Thyroid hormones have an important role in the growth and development of various tissues including the kidney, which is the major site of renin release and the consequent angiotensin and aldosterone formation. Therefore any derangement in thyroid function can result in abnormal functioning in the renin-angiotensin-aldosterone system. The current study was undertaken to find the impact of using a direct renin inhibitor (Aliskiren) and an angiotensin-converting enzyme inhibitor (Fosinopril) on the components of the renin-angiotensin-aldosterone system (RAAS) in rats with thyroid dysfunctions. Method. Forty-two male albino rats were divided into three subgroups. First group (6 rats) served as control. Second group (18 rats) served as hyperthyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Third group (18 rats) served as hypothyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Induction of hyperthyroidism and hypothyroidism was done through daily oral administration of L-Thyroxine and Propylthiouracil, respectively. On day 40 of the study, the rats were sacrificed and blood was collected for estimation of renin, angiotensin I, angiotensin II, aldosterone, TSH, T3, and T4. The collected blood samples were also used for estimation of levels blood urea, serum creatinine, liver enzymes, and serum electrolytes. Blood pressure and urine collection were done on days 1 and 40. The collected urine was used for estimation of urine flow, sodium excretion, and potassium excretion rates. Results. In hypothyroid induced rats, serum renin level dropped as expected, while the use of Aliskiren and Fosinopril on these hypothyroid rats raised renin level due to the feedback mechanism. Both angiotensin I and II were significantly (P <0.05) lower than normal levels in the hypothyroid rats, unlike the level of aldosterone, which was higher than normal level. There was nonsignificant lowering in BP (systolic, diastolic, and mean BP) in the hypothyroid rats. Treatment of these rats with Aliskiren and Fosinopril did not lower the blood pressure more than normal when compared to the hypothyroid group. The hypothyroid rats also showed a decrease in level of serum creatinine. In hyperthyroid rats, there was a rise in levels of serum renin, angiotensin II, and aldosterone; nevertheless, the increase in angiotensin I level was significant. The use of Aliskiren and Fosinopril increased the level of renin nonsignificantly (decreased angiotensin I significantly). Hyperthyroid rats showed a significant increase in systolic, diastolic, and mean blood pressure. Both Aliskiren and Fosinopril increased urine flow, Na+   excretion, and K+ excretion rates. Aliskiren was better at reducing the high blood pressure. Conclusion. Aliskiren and Fosinopril in hyperthyroid rats decreased serum angiotensin I, angiotensin II, and aldosterone. Blockade of renin and inhibition of angiotensin-converting enzyme both resulted in a rebound increase in level of renin in hypothyroid rats. Aliskiren is better at controlling blood pressure in hyperthyroid rats. Urine flow, sodium excretion, and potassium excretion rates were improved by the use of Aliskiren and Fosinopril in hyperthyroid rats.

scholarly journals Rosiglitazone, a Ligand to PPARγ, Improves Blood Pressure and Vascular Function through Renin-Angiotensin System Regulation

PPAR Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
María Sánchez-Aguilar ◽  
Luz Ibarra-Lara ◽  
Leonardo Del Valle-Mondragón ◽  
María Esther Rubio-Ruiz ◽  
Alicia G. Aguilar-Navarro ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
In Silico ◽  
Vascular Function ◽  
Renin Angiotensin System ◽  
Dependent Manner ◽  
Insulin Sensitizer ◽  
Angiotensin System ◽  
Renin Angiotensin

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to act as insulin sensitizer and exert cardiovascular actions. In this work, we hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure through modulation of angiotensin-converting enzyme (ACE)-type 2 (ACE2)/angiotensin-(1-7)/angiotensin II type-2 receptor (AT2R) axis in an experimental model of high blood pressure. We carried on experiments in normotensive (Sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham and AoCo rats were treated 7 days with vehicle (V), RGZ (5 mg/kg/day), or RGZ+BADGE (120 mg/kg/day) post-coarctation. We measured blood pressure and vascular reactivity on aortic rings, as well as the expression of renin-angiotensin system (RAS) proteins. We found that RGZ treatment in AoCo group decreases blood pressure values and improves vascular response to acetylcholine, both parameters dependent on PPARγ-stimulation. RGZ lowered serum angiotensin II (AngII) but increased Ang-(1-7) levels. It also decreased 8-hydroxy-2′-deoxyguanosine (8-OH-2dG), malondialdehyde (MDA), and improved the antioxidant capacity. Regarding protein expression of RAS, RGZ decreases ACE and angiotensin II type 1 receptor (AT1R) and improved ACE2, AT2R, and Mas receptor in AoCo rats. Additionally, an in silico analysis revealed that 5′UTR regions of RAS and PPARγ share motifs with a transcriptional regulatory role. We conclude that RGZ lowers blood pressure values by increasing the expression of RAS axis proteins ACE2 and AT2R, decreasing the levels of AngII and increasing levels of Ang-(1-7) in a PPARγ-dependent manner. The in silico analysis is a valuable tool to predict the interaction between PPARγ and RAS.

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