DOCSLIB.ORG

Comparison of Active Renin Concentration and Plasma Renin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparison of Active Renin Concentration and Plasma Renin European Journal of Endocrinology (2004) 150 517–523 ISSN 0804-4643 CLINICAL STUDY Comparison of active renin concentration and plasma renin activity for the diagnosis of primary hyperaldosteronism in patients with an adrenal mass Nicole Unger1, Ingo Lopez Schmidt1, Christian Pitt4, Martin K Walz4, Thomas Philipp2, Klaus Mann1,3 and Stephan Petersenn1 1 Division of Endocrinology, Medical Center, 2 Division of Nephrology and Hypertension, Medical Center, 3 Department of Clinical Chemistry, University of Essen and 4 Department of Surgery and Centre of Minimally Invasive Surgery, Kliniken Essen-Mitte, Essen, Germany (Correspondence should be addressed to S Petersenn, Division of Endocrinology, Medical Center, University of Essen, Hufelandstr. 55, 45122 Essen, Germany; Email: [email protected]) Abstract Objective: Plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio is an established screening test for primary hyperaldosteronism. Due to the increased recognition of adrenal incidentalomas, reliable parameters are required. Determination of active renin concentration (ARC) in contrast to PRA offers advantages with regard to processing and standardization. The present study compared PRA and ARC under random conditions to establish thresholds for the diagnosis of primary hyperaldosteronism. Design and methods: Fifty patients with various adrenal tumors, including ten patients with aldo- sterone-secreting adrenal adenomas, as well as ten hypertensive patients and 23 normotensive volunteers were studied. PAC and PRA were measured by radioimmunoassay. ARC was determined by an immunoluminometric assay. Results: Receiver operating curve (ROC) analysis suggested a PAC to ARC ratio threshold of 90 ((ng/l)/(ng/l)) (sensitivity 100%, specificity 98.6%) and a ratio threshold of 62 by additional consider- ation of PAC $200 ng/l (sensitivity 100%, specificity 100%) for the diagnosis of aldosterone-secreting adrenal adenomas. Conclusions: A PAC to ARC ratio of $62 in patients with PAC levels $200 ng/l is a reliable screening method for primary hyperaldosteronism in patients with an aldosterone-producing adenoma under random conditions. Because of its advantages with regard to probe processing and its independence from endogenous angiotensinogen levels, ARC may be preferred to PRA. European Journal of Endocrinology 150 517–523 Introduction either PAC or PRA, the PAC to PRA ratio seems to be independent of diurnal and day-to-day variations, salt Primary hyperaldosteronism is classically characterized intake and diuretics. It was demonstrated as a reliable by a combination of hypertension, hypokalemia, and convenient screening tool for ambulatory con- suppressed renin and an elevated non-suppressible ditions, independent of body posture (6). However, a plasma aldosterone concentration. Measurement of recent study revealed a low reproducibility of the ratio these single parameters does not allow a reliable diag- in patients with an aldosterone-producing adrenal ade- nosis. Normokalemia is noted in patients with primary noma under random conditions (7). PRA is determined hyperaldosteronism (1–3), as well as suppressed renin by radioimmunological measurement of angiotensin-1 in hypertensive patients (4, 5). Due to improved generated from angiotensinogen during in vitro incu- methods in computed tomography (CT) or magnetic bation with plasma renin. However, determination is resonance imaging (MRI), adrenal incidentalomas are limited to physiological angiotensinogen levels. Con- increasingly found. Accurate parameters to distinguish ditions with decreased angiotensinogen levels (e.g. aldosterone-secreting adrenal adenomas from other liver cirrhosis, severe cardiac failure) result in the functioning or non-functioning adrenal masses are underestimation of renin (8, 9). In contrast, estrogen therefore required. treatment increases angiotensinogen levels, resulting The plasma aldosterone concentration (PAC) to in an overestimation of renin (10, 11). The lack of stan- plasma renin activity (PRA) ratio was suggested as a dardization is another methodical disadvantage. screening tool for the diagnosis of primary hyperaldos- Processing of plasma samples, especially in regard to teronism (1). In contrast to single measurement of incubation time, pH and dilution varies among different q 2004 Society of the European Journal of Endocrinology Online version via http://www.eje.org Downloaded from Bioscientifica.com at 09/30/2021 11:59:54PM via free access 518 N Unger and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2004) 150 Table 1 Clinical characterization of the population studied. Values are means^S.D. Diagnosis No. of patients Age (years) Sex (male/female) Tumor size (cm) Aldosterone-secreting adenoma 10 51.4^13.3 3/7 1.8^0.6 Cortisol-secreting adenoma 7 43.7^12.5 0/7 3.3^0.8 Pheochromocytoma 12 49.3^16.5 6/6 3.8^2.5 Non-functioning adrenal mass (NFM) 21 51.9^12.6 10/11 3.9^2.6 Essential hypertension 10 41.6^11.4 6/4 na Healthy volunteers 23 34.2^12.2 10/13 na Total 83 44.6^14.6 35/48 na na, not available. laboratories. In patients with suppressed renin, the removed. The diagnosis was postoperatively confirmed ratio is clearly dependent on the lower detection limit. by histological and immunohistochemical examin- An assay sensitivity of 0.5 ng/ml per hour for a PRA ations as well as clinical follow-up. assay compared with 0.1 ng/ml per hour for another Controls included ten patients with essential hyper- assay results in an unequivocal lower PAC to PRA ratio. tension and 23 healthy normotensive volunteers To avoid these disadvantages, generation of mono- taking an ad libitum sodium diet. In patients with essen- clonal antibodies against active renin allowed direct tial hypertension, endocrine disorders were excluded by measurement of active renin concentration (ARC) inde- the following tests: primary hyperaldosteronism was pendent from angiotensinogen levels. Standardization excluded by a normal PAC and PAC to PRA ratio; Cush- of ARC measurement by calibration against a WHO ing’s syndrome was investigated by midnight plasma standard enables improved comparability among differ- cortisol levels and a dexamethasone suppression test; ent laboratories. The present study compared PRA and pheochromocytoma was excluded by normal meta- ARC under random conditions to investigate the use of nephrines and urinary catecholamines. Furthermore, ARC for the diagnosis of primary hyperaldosteronism in renal artery stenosis was excluded by MRI and/or patients with aldosterone-producing adenomas. duplex ultrasound in nine of ten patients. In total, 83 subjects were included in this prospective study (perti- nent data are given in Table 1). Materials and methods At the time of investigation, patients with an aldos- Subjects terone-secreting adrenal adenoma, patients with pheo- chromocytoma, and patients with hypertension were Fifty patients with a current adrenal mass were on various antihypertensive medications, as well as grouped into four categories: ten aldosterone-secreting nine hypertensive patients with non-functioning adre- adrenal adenomas; seven cortisol-secreting adrenal nal adenomas. Three of ten patients with an aldoster- adenomas (one subclinical and six overt Cushing’s syn- one-producing adenoma received spironolactone dromes), 12 pheochromocytomas; and 21 non-func- preoperatively (Table 2). tioning adrenal masses (17 non-functioning Blood samples were drawn from patients in an adenomas, two cysts, one metastasis of bronchial carci- upright body position from a forearm vein between noma, one myeololypoma). The diagnoses were made 0800 h and 0900 h. The study protocol was approved preoperatively by appropriate biochemical parameters by the local ethical committee and informed consent in combination with evidence of an adrenal mass on was given by all patients. CT or MRI. Primary hyperaldosteronism due to an adre- nal adenoma was diagnosed by a plasma aldosterone to Assays renin activity ratio $300 (ng/l to ng/ml per h) and PA C $200 ng/l (12) and in part confirmed by increased PAC was measured by RIA (Byk & DiaSorin, Dietzen- urinary aldosterone-18-glucuronide excretion, saline bach, Germany). The normal range in an upright pos- infusion test, adrenal vein sampling and/or postural ition was 100–350 ng/l. Assay sensitivity was 50 ng/l stimulation test. Four patients showed a normokaliemic and assay variability was determined by within-assay hyperaldosteronism. In these ten patients, CT or MRI coefficients of variation (CV) of 11.2% for 73 ng/l and revealed a unilateral adrenal mass. Clinical follow-up 8.2% for 308 ng/l and between-assay CV values of was carried out in five patients demonstrating a nor- 17.7% for 73 ng/l, 10.4% for 208 ng/l and 6.6% for malized PAC to PRA ratio postoperatively. Because of 454 ng/l. the limitations of the screening parameters, patients PRA was also determined by RIA (Byk & DiaSorin). with mild hyperaldosteronism might have been The normal range in an upright position was 1.8– undiagnosed. 6.3 ng/ml per hour. Assay sensitivity was 0.1 ng/ml Except for five non-functioning adenomas with a size per hour. Within-assay CV values were 7.5% for less than 3 cm, all adrenal masses were subsequently 0.17 ng/ml per hour, 5.4% for 8.8 ng/ml per hour www.eje.org Downloaded from Bioscientifica.com at 09/30/2021 11:59:54PM via free access EUROPEAN JOURNAL OF ENDOCRINOLOGY (2004) 150 Diagnosis of primary hyperaldosteronism 519 Table 2 Medication in patients with hypertension. Aldosterone-secreting Cortisol-secreting Essential Medication adenoma adenoma Pheochromocytoma NFM hypertension a blockers 2 — 6 1 1 b blocker 6 4 1 3 7 Ca-channel blocker 4 2 2 5 7 ACE inhibitors 4 1 2 4 3 AT1-receptor antagonists — 2 1 2 1 Diuretics 2 1 1 2 1 Clonidin 1 — — 1 1 Spironolactone 3 — — — — ACE, angiotensin converting enzyme; AT1, angiotensin-A. and 9.9% for 13.5 ng/ml per hour. Between-assay CV analysis suggested a ratio threshold value of 680 (sen- values were 7.7% for 2.6 ng/ml per hour, 8.1% for sitivity 100%, specificity 91.8%, area under the curve 8.6 ng/ml per hour and 11.5% for 13.0 ng/ml per hour.
Load more

Recommended publications
  • Aldosterone and Parathyroid Hormone: Evidence for a Clinically Relevant Relationship
    Journal of Endocrinology and Thyroid Research ISSN: 2573-2188 Review Article J Endocrinol Thyroid Res Volume 4 Issue 3 - May 2019 Copyright © All rights are reserved by Vismay Naik DOI: 10.19080/JETR.2019.04.555637 Aldosterone and Parathyroid Hormone: Evidence for a Clinically Relevant Relationship Vismay Naik* PG Diploma in Endocrinology and Diabetes, Ashirvad Heart and Diabetes Centre, India Submission: April 13, 2019; Published: May 06, 2019 *Corresponding author: Vismay Naik, MD, MRCP(UK), PG Diploma in Endocrinology and Diabetes, Ashirvad Heart and Diabetes Centre, India Introduction hyperparathyroidism due to increased renal and faecal calcium A ‘new endocrine axis’, involving the bi-directional relati- excretion. PTH is increased as a result of the MR (mineralocorticoid onship between the parathyroid hormone (PTH) and the renin– receptor) mediated calciuretic and magnesiuretic effects, with a angiotensin–aldosterone system (RAAS) has been established trend towards hypocalcemia, hypomagnesemia and the direct recently. Individually these have long been recognized, althou- effects of aldosterone on parathyroid cells via binding to the MR. gh it is only in recent times that we are realizing the interplay Moreover, the angiotensin II receptor is expressed by human between the two and the corresponding effects this has on the parathyroid tissue, and angiotensin may therefore directly physiological and pathological roles within the body. Other cal- stimulate PTH secretion [6]. ciotropic hormones such as Vitamin D are also impacting on this relationship [1]. This report aims to highlight the cyclic nature of RAAS and Vitamin D these relationships, through the physiological pathways, which Aldosterone acts through the mineralocorticoid receptor, will then lead into pathological disease in multiple areas such as which belongs to the same superfamily of nuclear receptors as heart failure, cardiovascular health and bone homeostasis.
    [Show full text]
  • Hypertension: Shall We Focus on Adipose Tissue?
    www.jasn.org EDITORIALS Hypertension: Shall We Focus associated with incident hypertension among women with- out diabetes. The authors prospectively studied 872 women on Adipose Tissue? without diabetes or hypertension from the Nurses’ Health Study. After a follow-up of 14 years, 361 (41.4%) women Simona Bo and Paolo Cavallo-Perin developed hypertension. Plasma resistin values were signif- Department of Internal Medicine, University of Turin, Turin, Italy icantly associated with incident hypertension: The highest resistin tertile conferred a 75% higher risk for hypertension J Am Soc Nephrol 21: 1067–1068, 2010. doi: 10.1681/ASN.2010050524 than the lowest (relative risk 1.75; 95% confidence interval 1.19 to 2.56). The relative risk did not substantially change after adjustment for multiple potential metabolic and nu- Adipose tissue is an active endocrine organ that produces sub- tritional confounding factors and for other adipokines. The stances having local and systemic actions on blood vessels, kid- risk was greater among older women. In a secondary analy- neys, and the heart. Leptin, adiponectin, resistin, angiotensin sis, inflammatory and endothelial biomarkers were mea- ␣ II, adipsin, TNF- , IGF-1, plasminogen-activator inhibitor 1, sured in a subset of women. Resistin levels were significantly and prostaglandins compose an incomplete list.1 associated with both groups of biomarkers. After further Resistin, an adipokine belonging to the cysteine-rich secre- adjustment for C-reactive protein, IL-6, soluble TNF recep- tory protein family, was described as an adipocyte-derived tor 2, intercellular adhesion molecule 1, vascular adhesion polypeptide that links obesity and insulin resistance in mice2; molecule 1, and E-selectin, resistin concentrations re- however, striking differences in the genomic organization and mained positively associated with an increased risk for inci- cellular source of resistin in rodents versus humans and the dent hypertension.
    [Show full text]
  • Why Is Plasma Renin Activity Lower in Populations of African Origin?
    Journal of Human Hypertension (2001) 15, 17–25 2001 Macmillan Publishers Ltd All rights reserved 0950-9240/01 $15.00 www.nature.com/jhh REVIEW ARTICLE Why is plasma renin activity lower in populations of African origin? GA Sagnella Blood Pressure Unit, St George’s Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK Plasma renin activity is significantly lower in black the molecular level suggests that the lower PRA may people compared with whites independent of age and arise from gene variation in the renal epithelial sodium blood pressure status. The lower PRA appears to be due channel. The functional significance of the lower PRA in to a reduction in the rate of secretion of renin but the relation to the different pattern of cardiovascular and exact mechanistic events underlying such differences in renal disease between blacks and whites remains renin release between blacks and whites are still not unclear. Moreover, direct investigations of pre-treat- fully understood. Nevertheless, given the paramount ment renin status in hypertensive blacks in relation to importance of the renin-angiotensin system in the con- blood pressure response have demonstrated that the trol of sodium balance, a most likely explanation is that pre-treatment PRA is not a good index of subsequent the lower renin is a consequence of differences in renal blood pressure response to pharmacological treatment. sodium handling between blacks and whites. The lower Nevertheless, the blood pressure reduction to short PRA does not reflect differences in dietary sodium term sodium restriction is greater in blacks compared intake but the evidence available suggests that the low with whites and, in the black subjects, the greater PRA could be part of the corrective mechanisms reduction in blood pressure to sodium restriction designed to maintain sodium balance in the presence appears to be related, at least in part, to the decreased of an increased tendency for sodium retention in black responsiveness of the renin-angiotensin system.
    [Show full text]
  • High and Non-Suppressible Plasma Renin Activity in a Patient with Aldosterone Producing Adenoma: Pathophysiologic and Diagnostic Implications
    Journal of Human Hypertension (1999) 13, 75–78 1999 Stockton Press. All rights reserved 0950-9240/99 $12.00 http://www.stockton-press.co.uk/jhh CASE REPORT High and non-suppressible plasma renin activity in a patient with aldosterone producing adenoma: pathophysiologic and diagnostic implications E Shyong Tai and PHK Eng Department of Endocrinology, Singapore General Hospital, Singapore We describe a case of primary aldosteronism due to an possible pathophysiological causes of a rise in PRA in aldosterone producing adenoma with high and non-sup- this clinical setting and suggest that underlying arteri- pressible plasma renin activity (PRA). She had sup- olar disease due to prolonged hypertension may be the pressed PRA at initial diagnosis. This rose above the cause of increased and non-suppressible PRA in pri- reference range for normal individuals over a period of mary aldosteronism. 7 years with untreated hypertension. We discuss the Keywords: primary aldosteronism; plasma renin activity; diagnosis Introduction Case report Primary aldosteronism is classically associated with Our patient was a 34-year-old woman who was hypertension, hypokalaemia and suppressed plasma found to have hypertension during the fifteenth renin activity (PRA). Most cases are due to an aldo- week of pregnancy. Plasma aldosterone was sterone producing adenoma (APA). We present a 2039 pmol/l, PRA Ͻ0.15 ␮g/l/h and a diagnosis of case of prolonged, untreated, primary aldosteronism primary aldosteronism was made. Following the due to an APA. She had suppressed PRA at the time delivery of her child, she defaulted follow-up and of diagnosis, which became elevated and non-sup- was not treated with any antihypertensives nor pot- pressible by intravenous salt loading.
    [Show full text]
  • Aldosterone-Renin Ratio (Arr)
    RENIN -ALDOSTERONE PROFILING: ALDOSTERONE-RENIN RATIO (ARR) 1. Obtain a morning specimen for serum aldosterone (redtop tube) and plasma renin (lavender-top) tube from an upright patient sitting for a period of 15 min prior to (being seated for) blood drawing. Fasting is not required and no salt restriction is necessary. 2. Spironolactone. The ratio cannot be assessed in patients receiving spironlactone. If primary aldosteronism (PA) is suspected in a patient receiving this drug, treatment should be discontinued for 4-6 weeks (1). 3. Hypokalemia should be corrected before ARR is measured as a low K will lower aldosterone and can lead to a falsely negative ARR (1). 4. Preferred antihypertensives that have a minimal effect on the ARR are doxazozin (Cardura), prazosin (Minipress), verapramil slow release, or hydralazine, singly or in combination for one month before sampling (1). 5. False-positive ARR: Beta-blockers, clonidine, methyldopa, and NSAID’s lower levels of renin and can cause a falsely positive ARR (1). A minimum 3-day cessation prior to sampling is recommended (3). The renin direct assay is also lower in patients on oral contraceptives and hormone replacement therapy potentially causing the ARR to be falsely increased. Measurement of plasma renin activity is preferred in this situation, calculating the aldosterone/PRA ratio (positive if >20/1). 6. False-negative ARR: Diuretics cause false negatives by causing K loss lowering aldosterone and stimulating renin through volume loss. Angiotensin blockers (ARB’s), ACE inhibitors, and some calcium channel blockers raise renin and can cause false negatives (1). A minimum three-day cessation prior to sampling is recommended (3).
    [Show full text]
  • The Renin-Angiotensin System and the Heart: a Historical Review Heart: First Published As 10.1136/Hrt.76.3 Suppl 3.7 on 1 November 1996
    Heart (Supplement 3) 1996;76:7-12 7 The renin-angiotensin system and the heart: a historical review Heart: first published as 10.1136/hrt.76.3_Suppl_3.7 on 1 November 1996. Downloaded from Stephen J Cleland, John L Reid Early observations on a possible link effect but was in fact an enzyme. The names between the kidney and the "hypertensin""l and "angiotonin"12 were given cardiovascular system to the pressor substance formed from the renin In 1836 an English clinician Richard Bright substrate by the enzymatic action of renin. observed that patients dying with contracted Subsequently, it was agreed that the term kidneys often had a hard, full pulse and cardiac "angiotensin" would be used to describe this hypertrophy.' In 1889 Brown-Sequard, the substance. During this period the potential for "father" of endocrinology, showed that injec- pathological effects of renin was recognised. tions of extracts from guinea pig testicles were Winternitz described necrotising arteriolar able to produce systemic effects of vigour and lesions in animals which had undergone renal the perception of rejuvenation.2 On this back- artery ligation and also in nephrectomised ani- ground, in 1896 the Finnish physiologist mals which had been given kidney extracts.'3 Robert Tigerstedt and his student Per Finally, the relevance of renal control of blood Bergman began to explore the possibility that pressure in man was described by Young who, kidney extracts from rabbits may have some in 1936, cured a case of malignant hyperten- systemic effects on the cardiovascular system. sion by removing an ischaemic kidney.'4 In 1898 their classic paper was published showing that intravenous injection of these renal extracts exerted a pressor effect.
    [Show full text]
  • Plasma Renin Activity and Pro-B-Type Natriuretic Peptide Levels in Different Atrial Fibrillation Types
    Original Investigation Özgün Araşt›rma 317 Plasma renin activity and pro-B-type natriuretic peptide levels in different atrial fibrillation types Farklı atriyal fibrilasyon türlerinde plazma renin aktivitesi ve pro-B-tipi natriüretik peptit düzeyleri Abdullah Doğan, Ömer Gedikli1, Mehmet Özaydın, Gürkan Acar2 Department of Cardiology, Faculty of Medicine, Süleyman Demirel University, Isparta 1Department of Cardiology, Faculty of Medicine, Karadeniz Technical University, Trabzon 2Department of Cardiology, Faculty of Medicine, Sütçü Imam University, Kahramanmaraş, Turkey ABSTRACT Objective: Renin-angiotensin system may be activated during atrial fibrillation (AF). Our aim was to evaluate plasma renin activity (PRA) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with different AF types who had normal left ventricular (LV) systolic function. Methods: This cross-sectional study included 97 patients with recent (≤7 days), persistent (7 days to 12 months) and permanent AF (>12 months), and age- and sex-matched 30 controls with sinus rhythm. Plasma levels of PRA and NT-pro-BNP were measured and presented as median (25th-75th percentiles). Echocardiographic examination was performed in all population. Variance and logistic regression analyses were also used for multiple comparisons and independent predictors, respectively. Results: Median NT-proBNP levels were higher in overall patients with AF than in controls [114 (63-165) vs 50 (38-58) pg/ml, p<0.001), but PRA level was comparable in both groups. Similarly, NT-proBNP levels were also higher in all subtypes of AF compared with controls (p<0.05). In addition, there was a significant difference in NT-proBNP level among recent, persistent and permanent AF subtypes (p=0.001).
    [Show full text]
  • Role of the Renin-Angiotensin-Aldosterone
    International Journal of Molecular Sciences Review Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension Natalia Muñoz-Durango 1,†, Cristóbal A. Fuentes 2,†, Andrés E. Castillo 2, Luis Martín González-Gómez 2, Andrea Vecchiola 2, Carlos E. Fardella 2,* and Alexis M. Kalergis 1,2,* 1 Millenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330025 Santiago, Chile; [email protected] 2 Millenium Institute on Immunology and Immunotherapy, Departamento de Endocrinología, Escuela de Medicina, Pontificia Universidad Católica de Chile, 8330074 Santiago, Chile; [email protected] (C.A.F.); [email protected] (A.E.C.); [email protected] (L.M.G.-G.); [email protected] (A.V.) * Correspondence: [email protected] (C.E.F.); [email protected] (A.M.K.); Tel.: +56-223-543-813 (C.E.F.); +56-223-542-842 (A.M.K.) † These authors contributed equally in this manuscript. Academic Editor: Anastasia Susie Mihailidou Received: 24 March 2016; Accepted: 10 May 2016; Published: 23 June 2016 Abstract: Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition.
    [Show full text]
  • Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD
    International Journal of Molecular Sciences Review Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD Anastasia V. Poznyak 1,* , Dwaipayan Bharadwaj 2,3, Gauri Prasad 3, Andrey V. Grechko 4, Margarita A. Sazonova 5 and Alexander N. Orekhov 1,5,6,* 1 Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia 2 Academy of Scientific and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi 110067, India; [email protected] 3 Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India; [email protected] 4 Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 14-3 Solyanka Street, 109240 Moscow, Russia; [email protected] 5 Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia; [email protected] 6 Institute of Human Morphology, 3 Tsyurupa Street, 117418 Moscow, Russia * Correspondence: [email protected] (A.V.P.); [email protected] (A.N.O.) Abstract: Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin–angiotensin–aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to Citation: Poznyak, A.V.; Bharadwaj, the recruitment of inflammatory cells to the injured site and stimulates the production of various D.; Prasad, G.; Grechko, A.V.; cytokines, such as IL-6, TNF-a, and COX-2.
    [Show full text]
  • Effects of Moxonidine on the Sympathetic Nervous System
    Journal of Clinical and Basic Cardiology An Independent International Scientific Journal Journal of Clinical and Basic Cardiology 2004; 7 (1-4), 19-25 Effects of Moxonidine on the Sympathetic Nervous System, Blood Pressure, Plasma Renin Activity, Plasma Aldosterone, Leptin, and Metabolic Profile in Obese Hypertensive Patients Sanjuliani AF, Francischetti EA, Genelhu de Abreu V Ueleres Braga J Homepage: www.kup.at/jcbc Online Data Base Search for Authors and Keywords Indexed in Chemical Abstracts EMBASE/Excerpta Medica Krause & Pachernegg GmbH · VERLAG für MEDIZIN und WIRTSCHAFT · A-3003 Gablitz/Austria ORIGINAL PAPERS, CLINICAL CARDIOLOGY Moxonidine in Obese Hypertensive Patients J Clin Basic Cardiol 2004; 7: 19 Effects of Moxonidine on the Sympathetic Nervous System, Blood Pressure, Plasma Renin Activity, Plasma Aldosterone, Leptin, and Metabolic Profile in Obese Hypertensive Patients A. F. Sanjuliani, V. Genelhu de Abreu, J. Ueleres Braga, E. A. Francischetti Obesity accounts for around 70 % of the patients with primary hypertension. This association accentuates the risk of cardiovascular disease as it is frequently accompanied by the components of the metabolic syndrome. Clinical, epidemiological and experimental studies show an association between obesity-hypertension with insulin resistance and increased sympathetic nervous system activity. We conducted the present study to evaluate in forty obese hypertensives of both genders, aged 27 to 63 years old, the chronic effects of moxonidine – a selective imidazoline receptor agonist – on blood pressure, plasma catecholamines, leptin, renin-angiotensin aldosterone system and components of the metabolic syndrome. It was a randomized parallel open study, amlodipine was used as the control drug. Our results show that moxonidine and amlodipine significantly reduced blood pressure without affecting heart rate when measured by the oscillometric method and with twenty-four-hour blood pressure monitoring.
    [Show full text]
  • The Renin-Angiotensin-Aldosterone System and The
    36 Heart (Supplement 3) 1996;76:36-44 The renin-angiotensin-aldosterone system and the cardiac natriuretic peptides Heart: first published as 10.1136/hrt.76.3_Suppl_3.36 on 1 November 1996. Downloaded from A Mark Richards Natriuretic peptides and the renin- functions as a "clearance receptor", removing angiotensin-aldosterone system (RAAS) have natriuretic peptides from the circulation.5 reciprocal effects at multiple sites and in varied ANF and BNP stimulate cGMP production situations. They interact in health and cardio- through the NPR-A receptor. The NPR-B vascular disease to influence renal, endocrine, receptor is selective for CNP.6 The NPR-C and haemodynamic function and cardiovascu- (clearance receptor) binds all three of the lar cell growth. The atrial natriuretic peptide natriuretic peptides. Natriuretic peptides are (atrial natriuretic factor, ANF) discovered by also subject to clearance by enzymatic degra- De Bold in 19811 was cloned and sequenced dation. The neutral endopeptidase EC by molecular biological techniques in 1984.2 3A4'24'11 contributes to ANF clearance (and The related peptides, brain natriuretic peptide to a lesser extent BNP clearance) in humans.7 (BNP) and C-type natriuretic peptide (CNP), The biochemistry of natriuretic peptides is fur- were sequenced in 1988 and 1990, respec- ther detailed in a recent review.8 tively.34 The mature forms of the peptides The focus of the present review is the inter- share a common core structure consisting of a action of the cardiac natriuretic peptides with 17-amino acid ring with some conservation of the RAAS. Studies in humans will be amino acid residues between peptides (fig reviewed, with additional information from in 1).24 ANF is present at high concentrations in vitro or intact animal experiments where atrial tissue, and in lesser amounts in the cen- appropriate.
    [Show full text]
  • The Natriuretic Peptides System in the Pathophysiology of Heart Failure: from Molecular Basis to Treatment
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio della ricerca- Università di Roma La Sapienza Clinical Science (2016) 130, 57–77 doi: 10.1042/CS20150469 The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment Massimo Volpe*†, Marino Carnovali‡ and Vittoria Mastromarino* *Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, 00189 Rome, Italy †IRCCS Neuromed, 86077 Pozzilli, IS, Italy ‡Rehabilitation Department, A.O. “G. Salvini” 20024 Garbagnate Milanese, Milan, Italy Abstract After its discovery in the early 1980s, the natriuretic peptide (NP) system has been extensively characterized and its potential influence in the development and progression of heart failure (HF) has been investigated. HF is a syndrome characterized by the activation of different neurohormonal systems, predominantly the renin–angiotensin (Ang)–aldosterone system (RAAS) and the sympathetic nervous system (SNS), but also the NP system. Pharmacological interventions have been developed to counteract the neuroendocrine dysregulation, through the down modulation of RAAS with ACE (Ang-converting enzyme) inhibitors, ARBs (Ang receptor blockers) and mineralcorticoid antagonists and of SNS with β-blockers. In the last years, growing attention has been paid to the NP system. In the present review, we have summarized the current knowledge on the NP system, focusing on its role in HF and we provide an overview of the pharmacological attempts to modulate NP in HF: from the negative results of the study with neprilysin (NEP) inhibitors, alone or associated with an ACE inhibitor and vasopeptidase inhibitors, to the most recently and extremely encouraging results obtained with the new pharmacological class of Ang receptor and NEP inhibitor, currently defined ARNI (Ang receptor NEP inhibitor).
    [Show full text]