DOCSLIB.ORG

Effects of Corticotropin-Releasing Factor(CRF) on Aldosterone and 18-Hydroxycorticosterone in Essential Hypertension and Primary Aldosteronism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effects of Corticotropin-Releasing Factor(CRF) on Aldosterone and 18-Hydroxycorticosterone in Essential Hypertension and Primary Aldosteronism Endocrinol. Japon. 1987, 34(6), 809-819 Effects of Corticotropin-Releasing Factor(CRF) on Aldosterone and 18-Hydroxycorticosterone in Essential Hypertension and Primary Aldosteronism ISAMUMIYAMORI, SHUICHIROYASUHARA, TAKAOMATSUBARA, SEIYA OKAMOTO, MASATOSHIIKEDA, HIDEO KOSHIDA, TOSHIO MORISE, YOSHIYUTAKEDA, RYOYU TAKEDA AND PAUL VECSEI* The Second Department of Internal Medicine, School of Medicine, Kanazawa University and *Pharmacological Institute , Heidelberg University Abstract The effects of ovine corticotropin releasing factor(o-CRF) on plasma aldo- sterone, 18-OH-corticosterone(18-OHB), plasma adrenocorticotropin(ACTH) and cortisol were determined in eight patients with primary aldosteronism, six with aldosterone-producing adenoma(APA) and two with idiopathic hyperaldosteronism(IHA). The results were compared with those in six normal subjects and eleven patients with essential hypertension(EHT, 5with low renin and 6 with normal renin). In patients with APA, the peak plasma aldosterone and 18-OHB responses to 100μg iv of o-CRF(226%and 113% increase from baseline, respectively) were greater than those in EHT and normal subjects. The net integrated aldosterone and 18-OHB responses(840 ±156, and 419±121 ng/dl・hr, respectively) were also significantly greater (P<0.01) in APA than those in normals and EHT. In two patients with IHA, both the peak and net integrated aldosterone response were smaller than those in APA, in spite of nearly identical plasma ACTH and cortisol responses. These results suggest that augmented responses of mineralocorticoids to o-CRF may be characteristic of aldosteronism due to APA, mediated by CRF. induced ACTH, and possibly other proopiomelanocortin(POMC)-derived peptides. Regulation of aldosterone secretion in aldosteronism due to aldosterone producing primary aldosteronism has not been fully adenoma(APA), aldosterone appears to be clarified. Evidence so far indicates that the under the control of adrenocorticotropin control of aldosterone differs among the (ACTH), from observations of diurnal paral- subtypes of this syndrome. In primary lelism of plasma aldosterone and plasma cortisol(Kem et al., 1973), augmented aldo- Received December12, 1986 sterone responses to exogenous ACTH(Kem Address: The Second Department of Internal ｅt al., 1978, Espiner and Donald,1980) Medicine, School of Medicine, Kanazawa and the suppressibility of aldosterone pro- University, Takara-Machi13-1, Kanazawa920, Japan duction by dexamethasone administration, Endocrinol. Japon. 810 MIYAMORI et al. December 1987 although the functional heterogeneity of the in patients with primary aldosteronism than patients with APA was also reported(Went- essential hypertension(EHT) and that CRF ing et al., 1978). In primary aldosteronism administration may further contribute to due to idiopathic hyperaldosteronism(IHA), the differentiation of subtypes of primary aldosterone production appears partly de- aldosteronism. pendent on the renin-angiotensin system, and this is supported by findings that plasma aldosterone increases in response to the Materials and Methods renin stimulation produced by assuming an upright posture(Ganguly et al., 1973) or Eight patients with primary aldosteronism more directly, by the infusion of angiotensin (5 females, 3 males, aged 34-68 years old, 6 II which resulted in greater aldosterone patients with APA and 2 with IHA) and eleven response in patients with IHA(Wisgerhof patients with ETH(4 females, 7 males, aged 34- et al., 1978, Fraser et al., 1981). Con- 55 years old) were included in the study. All versely acute saline infusion for suppression of the patients were studied as inpatients of of plasma renin activity(PRA) has been clinical wards in Kanazawa University Hospital. One hundred microgram of ovine-CRF(o-CRF) used in the differentiation of the two forms (Peptide Institute, Inc., Osaka, Japan) which was of aldosteronism with varied success. Re- dissolved in sterile water and filtered through cently, corticotropin-releasing factor(CRF), millipore(Millipore Corporation, Bedford, Mass, now widely used to evaluate the hypo- U.S.A.) was administered to 6 healthy male thalamo-pituitary function(Nieman et al., volunteers(aged 22-35 years old) who were used 1986. Laue et al., 1987), has been shown as controls, and the results were compared with to stimulate aldosterone production in man those of patients. Secondary forms of hyper- tension were excluded by examination of normal (Hermus et al., 1984, Conaglen et al., 1984) serum potassium, plasma renin activity(PRA), by increasing ACTH secretion. CRF also aldosterone, urinary 17-OH-corticoids and urinary releases the POMC-derived pituitary pep- excretion of catecholamines and vanylyl man- tides, and the aldosterone-stimulating prop- delic acid(VMA) on two consecutive days. erties of these non ACTH pituitary peptides Intravenous pyelography was performed in all have recently been demonstrated in adeno- hypertensive patients; renal size and the excre- matous tissues from patients with primary tory patterns on urograms were normal on both sides. The diagnosis of low renin EHT was aldosteronism(Aurecchia et al., 1982, Schif- made using the criteria reported previously frin et al., 1983). The plasma levels of the (Takeda et al., 1982), and 5 were low renin and POMC-derived peptides in primary aldo- 6 were normal renin EHT. The differential steronism have been reported with conflict- diagnosis of glucocorticoid suppressible hyper- ing results(Gullner et al., 1983a, Griffing aldosteronism was made by administering 2 et al., 1985a, Griffing et al., 1985b) and mg/day of dexamethasone for 2 weeks to patients the role of non-ACTH pituitary hormones who were suspected of this type of hyperaldo- steronism(Oberfield., 1981). Dexamethasone for the control of aldosterone secretion has failed to suppress plasma aldosterone to normal been reviewed recently(Brownie and Peder- ranges, and serum potassium and blood pressure sen 1986). Patients with APA show rela- were not normalized. In two patients(T.I. 54 tively greater 18-OHB concentrations than years old, male, and A.S. 68 years old, female) those with IHA(Biglieri and Schambelan the diagnosis of IHA was made on the basis of 1979, Kem et al., 1985), a finding which high concentrations of plasma aldosterone in both may also be useful in differentiating the adrenal veins and the absence of a solitary ade- noma on CT scan of the adrenal glands. Other two conditions. It may be hypothesized, biochemical data, including low serum potassium therefore, that CRF will produce greater concentrations, suppressed renin in response to increases in plasma aldosterone and 18-OHB furosemide(80 mg, orally) and upright posture Vol.34, No.6 MINERALOCORTICOID RESPONSE TO CRF 811 for 2 hours, high plasma aldosterone concentra- was 10-50 pg/ml for blood withdrawn at 8 a.m. tions and hypertension with various degrees of The net integrated ACTH and corticosteroid metabolic alkalosis were nearly identical both secretory responses to o-CRF were expressed as in patients with APA and those with IHA. All the areas under the concentration-time curve the patients ingested a regular diet containing (AUC) from -15 to 90 min, minus the area 200 mEq of sodium and 60 maq of potassium corresponding to the mean of the two basal per day during hospitalization. All medications values, multiplied by 90 min. The study protocol were stopped for at least three weeks and was approved by the Human Study Committee smoking and drinking were prohibited for one of Kanazawa University. week prior to the study. After an overnight Statistical analysis was performed using Stu- fast, patients were kept supine for at least 30 min dent's t-test for comparison of within-group prior to the start of the injection. Plasma data for comparison between groups, analysis samples were withdrawn from an indwelling of variance. Data were shown as mean•}SEM catheter 15 min prior to, immediately before and in the text. 15, 30, 45, 60 and 90 min after o-CRF (100 pg, iv bolus) administration. The experiment was performed in the morning between 8 and 10 a.m. Results In four patients with APA, 100 pg of o-CRF injection was repeated three to ten weeks after 1. Changes in plasma ACTH, cortisol, and successful removal of the adenoma, when bio- aldosterone and 18-OHB in response to o-CRF chemical abnormalities and blood pressure re- in normal subjects and patients with EHT. covered. Plasma aldosterone and cortisol were measured by radioimmunoassay (RIA) as reported In normal volunteers the basal plasma previously (Takeda et al., 1976). Plasma 18-OHB ACTH level was 31.1+7.0 pg/ml and in- was also measured by RIA after separation from creased significantly to a peak level of 82.2 other steroids by celite column with ethylene ±13.0pg/ml(p<0.05)at 60min after ad- glycol: water (4: 1) using an antibody developed ministration of o-CRF. Plasma cortisol by Vecsei et al. (1982). Triethylamine (0.1%) also increased from a basal level of 12.4•} was added to all reagents to prevent ketalization 0.9 to 19.4•}1.4 pg/dl at 60 min (p<0.01). of 18-OHB. Normal values in healthy males were 24•}6 ng/dl. Plasma ACTH was also The basal plasma aldosterone and 18-OHB measured by RIA using an antibody to the levels were 9.4•}1.4 ng/dl and 28.6•}3.8 N-terminal end raised in rabbits (IgG Corp., hg/dl which increased to 13.5•}1.9 ng/dl Nashville, Tenn U.S.A.). Plasma samples for and 41.2 +2.0 ng/dl, respectively at 60 min ACTH were collected in pre-chilled polyethylene after o-CRF administration (Table 1). The tubes containing EDTA and Trasylol. The blood peak plasma aldosterone and 18-oHB in- was immediately centrifuged and the plasma was crements in normals were 43.6% and 44.1%, stored at -80•Ž until assayed. The extraction and concentration of ACTH was performed using respectively. There were no significant Sep-Pak C18 cartridges (Waters Associates, Inc., changes in PRA and blood pressure at any Mass U.S.A.) following the method described observation point.
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]
  • 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]
  • Interaction of Renin–Angiotensin–Aldosterone System and Parathyroid Hormone; a New Dilemma Hamid Nasri1*
    Open Access http://www.jparathyroid.com Journal of Journal of Parathyroid Disease 2014,2(2),65–66 News and Views Interaction of renin–angiotensin–aldosterone system and parathyroid hormone; a new dilemma Hamid Nasri1* arious investigations have been detected, Implication for health policy/practice/research/ parathyroid hormone (parathormone) has been medical education implicated in regulating the renin–angiotensin– It is possible that physiological interaction between Valdosterone system (1-3). The system of renin– the renin–angiotensin–aldosterone system and angiotensin–aldosterone, in turn, has been involved in parathormone exists, however, this interaction requires regulating the calcium-regulatory hormones such as further investigations for better treatment of chronic vitamin D and parathormone. In fact, inappropriate action kidney disease. of both parathyroid hormone and the renin–angiotensin– aldosterone system may negatively influence skeletal health and cardiovascular (2-6). Funding/Support The observational studies such as reduced bone mineral No funding from any source. density and a higher rate of osteoporosis in patients with primary hyperaldosteronism and an elevated parathormone References levels which are lowered after clinically indicated surgical 1. Atchison DK, Westrick E, Szandzik DL, Gordish or medical treatment in these patients, is a human evidence KL, Beierwaltes WH. Parathyroid hormone-related describing the positive association between renin– protein stimulates plasma renin activity via its angiotensin–aldosterone system activity and parathormone anorexic effects on sodium chloride intake. Am J (1-5). Likewise, Treatment with spironolactone therapy Physiol Endocrinol Metab 2012; 303(4): E457-63. is associated with lower fracture risk in heart failure 2. Brown JM, Williams JS, Luther JM, Garg R, Garza (3-7).
    [Show full text]