X

Download MR Aldosterone and blood pressure PowerPoint Presentation

SlidesFinder-Advertising-Design.jpg

Login   OR  Register
X


Iframe embed code :



Presentation url :

Home / Health & Wellness / Health & Wellness Presentations / MR Aldosterone and blood pressure PowerPoint Presentation

MR Aldosterone and blood pressure PowerPoint Presentation

Ppt Presentation Embed Code   Zoom Ppt Presentation

PowerPoint is the world's most popular presentation software which can let you create professional MR Aldosterone and blood pressure powerpoint presentation easily and in no time. This helps you give your presentation on MR Aldosterone and blood pressure in a conference, a school lecture, a business proposal, in a webinar and business and professional representations.

The uploader spent his/her valuable time to create this MR Aldosterone and blood pressure powerpoint presentation slides, to share his/her useful content with the world. This ppt presentation uploaded by slidesfinder in Health & Wellness ppt presentation category is available for free download,and can be used according to your industries like finance, marketing, education, health and many more.

About This Presentation

Slide 1 - ppt slide no 1 content not found
Slide 2 - ΥΠΟΔΟΧΕΑΣ ΑΛΑΤΟΚΟΡΤΙΚΟΕΙΔΩΝ ΧΑΡΑΚΤΗΡΙΣΤΙΚΑ & ΠΛΕΙΟΤΡΟΠΕΣ ΔΡΑΣΕΙΣ Κωνσταντίνος Π. Μακαρίτσης Παθολογική Κλινική Πανεπιστημίου Θεσσαλίας 23 Ιανουαρίου 2014
Slide 3 - Η αλδοστερόνη απομονώθηκε για πρώτη φορά το 1953 και παράγεται στη σπειροειδή ζώνη του φλοιού των επινεφριδίων. Μείζονα ερεθίσματα για έκκριση αλδοστερόνης: Αγγειοτενσίνη ΙΙ Επίπεδα του Κ+ του πλάσματος Η αλδοστερόνη αυξάνει την επαναρρόφηση Να+ και ύδατος από το τελικό άπω εσπειραμένο και τη φλοιώδη μοίρα του αθροιστικού σωληναρίου του νεφρού. ΕΙΣΑΓΩΓΗ
Slide 4 - ENaC NCCT NKCC2 NHEs N Engl J Med Aldosterone
Slide 5 - Sodium Channels and Transporters Approximately 2-3% of filtered sodium is reabsorbed in the cortical collecting tubule via the epithelial Na channel (ENaC). ENaC is composed of 3 subunits, α, β, γ. All 3 subunits are required for a fully functional channel.
Slide 6 - Aldosterone-Regulated Transport - Cortical Collecting Tubule
Slide 7 - Aldosterone-Regulated Transport - Cortical Collecting Tubule Amiloride Triamterene Spironolactone Eplerenone X X N Engl J Med 1999;340:1177-87.
Slide 8 - Sodium Channels and Transporters Regulation of Na reabsorption depends on the number of channels inserted in the cell membrane. Vasopressin (via increased cAMP) and aldosterone (via serum and glucocorticoid-regulated kinase [SGK]) increase the density of channels at the cell surface.
Slide 9 - Regulation of ENaC membrane expression Insulin MR α β γ
Slide 10 - Mineralocorticoid Receptor-MR Στοιχεία Παθοφυσιολογίας
Slide 11 - Η συγκέντρωση της αλδοστερόνης στο πλάσμα είναι πολύ μικρή (<1nmol/L) και κυκλοφορεί συνδεδεμένη με την αλβουμίνη σε ποσοστό περίπου 50%. Αντιθέτως, τα φυσικά γλυκοκορτικοειδή – κορτιζόλη και κορτικοστερόνη – κυκλοφορούν συνδεδεμένα με την τρανσκορτίνη (CBG) και την αλβουμίνη σε ποσοστό περίπου 95% Τα επίπεδα της κορτιζόλης στο πλάσμα είναι από 100-1000 φορές υψηλότερα από τα επίπεδα της αλδοστερόνης. Στοιχεία Παθοφυσιολογίας
Slide 12 - Στοιχεία Παθοφυσιολογίας Ο Mineralocorticoid Receptor-MR είναι μέλος της οικογένειας των πυρηνικών υποδοχέων των στεροειδών/θυρεοειδικών/ρετινοϊκών/λιπιδικών/ ”ορφανών” υποδοχέων, που απαρτίζεται από 49 μέλη στον άνθρωπο. Ο MR μεταβάλλει την έκφραση συγκεκριμένων γονιδίων, αλλά έχει δειχθεί ότι συμμετέχει και στις καλούμενες ταχείες μη γονιδιωματικές δράσεις (rapid non-genomic effects). Hypertension. 2011;57:1019-1025.
Slide 13 - Aldosterone signaling Hypertension. 2011;57:1019-1025. Rapid non-Genomic Effects Genomic Effects PI3K
Slide 14 - Στοιχεία Παθοφυσιολογίας Ο MR εκφράζεται στα επιθηλιακά κύτταρα νεφρού κατιόντος κόλου σιελογόνων και ιδρωτοποιών αδένων Ωστόσο, ο MR έχει εντοπιστεί και σε μη-επιθηλιακά κύτταρα ιπποκάμπου καρδιάς(καρδιακά μυϊκά κύτταρα, ενδοθηλιακά,ινοβλάστες, μακροφάγα) αγγείων (ενδοθηλιακά και λεία μυϊκά κύτταρα)
Slide 15 - Έχει διαπιστωθεί, ότι ο MR παρουσιάζει παρόμοια χημική συγγένεια ως προς τη δέσμευση της αλδοστερόνης και της κορτιζόλης. Πώς η αλδοστερόνη ενεργοποιεί επιλεκτικά τον MR στα επιθηλιακά κύτταρα, καθώς αφενός δεν υπάρχει εκλεκτικότητα στο επίπεδο του υποδοχέα και αφετέρου τα επίπεδα της κορτιζόλης στο πλάσμα είναι από 100-1000 φορές υψηλότερα από τα επίπεδα της αλδοστερόνης;;; Mineralocorticoid Receptor-MR Molecular and Cellular Endocrinology 350 (2012) 289–298.
Slide 16 - Η απάντηση στο ερώτημα αυτό προέκυψε με την ανακάλυψη του ρόλου του ενζύμου 11βHSD2 (11β-hydroxysteroid dehydrogenase type 2), το οποίο εκφράζεται σε υψηλές συγκεντρώσεις μαζί με τον MR στα επιθηλιακά κύτταρα, αλλά και στο τοίχωμα των αγγείων και στον πυρήνα της μονήρους δεσμίδας (NTS). Το ένζυμο αυτό (11βHSD2) καταλύει τη μετατροπή της κορτιζόλης σε κορτιζόνη, ενώ δεν επηρεάζει την αλδοστερόνη. Η κορτιζόνη δεν ενεργοποιεί τον MR, οπότε διευκολύνεται η επίδραση της αλδοστερόνης στον MR. Mineralocorticoid Receptor-MR Molecular and Cellular Endocrinology 350 (2012) 289–298.
Slide 17 - ppt slide no 17 content not found
Slide 18 - 11β-HSD2* * 11β-Hydroxy Steroid Dehydrogenase2 SAME Syndrome Glycyrrhizic acid Carvenoxolone Congenital Adrenal Hyperplasia CHIMERIC GENE GRA
Slide 19 - Hypertens Res 2004; 27: 781–789. Mineralocorticoid Receptor-MR
Slide 20 - Mineralocorticoid Receptor-MR It has been subsequently shown that under normal conditions most epithelial MRs are occupied (~ 90%), but not activated by normal levels of endogenous glucocorticoids. MR–glucocorticoid complexes are presumably held inactive under normal conditions by the obligate co-generation of high levels of NADH, shown to be an inhibitor of transcription by co-repressor activation in other transcriptional systems. Biochimica et Biophysica Acta 1802 (2010) 1188–1192.
Slide 21 - Mineralocorticoid Receptor-MR Under conditions of tissue damage, reactive oxygen species generation and intracellular redox change, cortisol becomes a mineralocorticoid receptor agonist, in the vessel wall and heart, mimicking the deleterious effects of elevated aldosterone inappropriate for salt status. Biochimica et Biophysica Acta 1802 (2010) 1188–1192.
Slide 22 - Aldosterone is postulated to have played a key role in the phylogenic transition from aquatic fishes to terrestrial tetrapods, given its major epithelial effects on sodium retention and potassium excretion. Thus, the aldosterone/MR pathway enabled animals to retain sodium in the body to sustain life on land, where there was little salt. In our modern industrialized societies, however, an abundance of salt and a pandemic of obesity synergistically cause inappropriate activation of the aldosterone/MR system, that causes salt-sensitive hypertension and cardiorenal disease. MR and Evolution Hypertension 2010;55:813-818.
Slide 23 - Clin Exp Nephrol (2010) 14:303–314. Phylogenetic perspectives on the aldosterone/MR system CVD
Slide 24 - High levels of aldosterone in response to dietary salt restriction, promotes renal sodium conservation, but has no cardiovascular consequences. When aldosterone is produced in inappropriate amounts for the level of sodium status, it results in excessive renal sodium retention, potassium wasting, hypertension, and cardiovascular damage. N Engl J Med. 2004;351:8-10. Effects of Aldosterone in Relation to Sodium Status
Slide 25 - Physiologic and Pathophysiologic Effects of Aldosterone on the Kidney and Heart in Relation to Dietary Salt levels N Engl J Med. 2004;351:8-10. High Low
Slide 26 - In primary aldosteronism and chronic high salt intake, aldosterone levels are inappropriate high for sodium status and aldosterone is clearly a cardiovascular risk factor. In essential hypertension and heart failure it might be cortisol which activates mineralocorticoid receptors. Thus, mineralocorticoid receptor activation, not aldosterone, is the risk factor. Is aldosterone a cardiovascular risk factor? Biochimica et Biophysica Acta 1802 (2010) 1188–1192.
Slide 27 - Cardiology in Review 2005;13:118–124. Deleterious actions of Increased MR Activation Increased MR Activation
Slide 28 - MR, Aldosterone and Blood Pressure
Slide 29 - Aldosterone secretion is raised in response to sodium deficiency. Secretion of endogenous ouabain is raised in response to sodium loading. The role of aldosterone is to retain sodium in the face of chronic deficiency. The role of endogenous ouabain is to excrete sodium, via a pressure natriuresis effect. Endogenous ouabain increases blood pressure. MR, Aldosterone and blood pressure
Slide 30 - Aldosterone secretion is raised in response to sodium deficiency. Secretion of endogenous ouabain is raised in response to sodium loading. The role of aldosterone is to retain sodium in the face of chronic deficiency. The role of endogenous ouabain is to excrete sodium, via a pressure natriuresis effect. Endogenous ouabain increases blood pressure. MR, Aldosterone and blood pressure
Slide 31 - It is possible that the blood pressure elevating effects of aldosterone reflect not only direct effects on the vessel wall but also sodium retention with the resultant elevation of endogenous ouabain secretion. The combined elevation of aldosterone and endogenous ouabain levels in response to salt/mineralocorticoid imbalance may thus be an explanation of the hypertension produced. MR, Aldosterone and blood pressure
Slide 32 - Pathways of salt-sensitive hypertension Nature Medicine, Nov 2004 NCX1 Ouabain ___
Slide 33 - N Engl J Med. 2007;356:1966-78. Ouabain ___ Aldosterone
Slide 34 - MR in vascular constriction and relaxation
Slide 35 - In all studies, the effects of Aldo are MR-dependent, implicating vascular MR in direct regulation of vascular tone. MR activation in vascular SMC and EC increases ROS and decreases bioavailable NO and thus would be expected to promote VSMC contraction by decreasing GC activity. MR in vascular constriction and relaxation Molecular and Cellular Endocrinology 350 (2012) 256–265. British Journal of Pharmacology (2011) 163 1163–1169.
Slide 36 - Interestingly, when Aldo is infused into vessels intraluminally to target the endothelium a vasodilator response was found, that required the presence of the endothelium, MR, and NO generation via NOS. Co-incubation with NOS inhibitors resulted in a loss of vasodilation and/or enhanced contraction, again implicating endothelial MR in vasodilation and SMC MR in vasoconstriction. MR in vascular constriction and relaxation Molecular and Cellular Endocrinology 350 (2012) 256–265. British Journal of Pharmacology (2011) 163 1163–1169.
Slide 37 - The effects of MR activation on vascular reactivity in “healthy” humans also remains somewhat controversial due to conflicting results from clinical studies with many demonstrating a constrictive response and some showing vascular relaxation. The discrepancies may be due to differences in the vascular health of the study participants in addition to differences in dose and duration of Aldo infusion. MR in vascular constriction and relaxation Molecular and Cellular Endocrinology 350 (2012) 256–265. British Journal of Pharmacology (2011) 163 1163–1169.
Slide 38 - When patients with underlying cardiovascular diseases are studied, including patients with atherosclerosis, heart failure, and hypertension, the data are quite consistent with MR-activation promoting increased systemic vascular resistance and reduced forearm blood flow. MR in vascular constriction and relaxation Molecular and Cellular Endocrinology 350 (2012) 256–265. British Journal of Pharmacology (2011) 163 1163–1169.
Slide 39 - MR in vascular constriction and relaxation
Slide 40 - Taken together, these data support that in healthy vessels, acute MR activation may evoke endothelium - dependent, NO - mediated vasodilation while, in the presence of endothelial dysfunction, vascular injury, or high vascular oxidative stress (as in patients with cardiovascular risk factors), MR activation promotes vasoconstriction. MR in vascular constriction and relaxation Molecular and Cellular Endocrinology 350 (2012) 256–265. British Journal of Pharmacology (2011) 163 1163–1169.
Slide 41 - MR and Vascular Oxidative Stress
Slide 42 - The interaction of ROS with NO also decreases the bioavailability of NO resulting in impaired EC-dependent vasorelaxation and the peroxinitrite formed can directly alter many vascular cell functions. Aldosterone also produces oxidative stress and endothelial dysfunction by decreasing the expression of G6PD, which reduces NADP+ to NADPH. MR, Aldosterone and Vascular Oxidative Stress Molecular and Cellular Endocrinology 350 (2012) 256–265. Clinical Science (2007) 113, 267–278.
Slide 43 - MR, Aldosterone and Vascular Oxidative Stress Molecular and Cellular Endocrinology 350 (2012) 256–265. Clinical Science (2007) 113, 267–278. peroxinitrite
Slide 44 - MR, Aldosterone and Vascular Oxidative Stress
Slide 45 - MR and Vascular Inflammation
Slide 46 - Direct activation of MR has been shown to promote inflammatory gene expression. MR activation promotes expression of: adhesion molecules ICAM1 and VCAM1 interleukin-16 cytotoxic T-lymphocyte-ass. Protein 4 Infusion of Aldo increased circulating IL-6 Treatment with spironolactone reduced MCP-1 and PAI-1 levels MR, Aldosterone and Vascular Inflammation Molecular and Cellular Endocrinology 350 (2012) 256–265.
Slide 47 - Vascular MR activation participates in the inflammatory response by up-regulating adhesion molecules, chemokines, cytokines, and growth factors that promote the recruitment and activation of inflammatory cells. MR, Aldosterone and Vascular Inflammation Molecular and Cellular Endocrinology 350 (2012) 256–265.
Slide 48 - MR and Vascular Remodeling
Slide 49 - Multiple animal models support that Aldo exacerbates vascular remodeling in association with endothelial damage in vivo and these effects are reversed by MR antagonists. Human studies have shown that patients with primary aldosteronism have significantly increased vascular medial thickness and narrowed vessel lumens compared to patients with similar degrees of essential hypertension and other forms of secondary hypertension. MR, Aldosterone and Vascular Remodeling Molecular and Cellular Endocrinology 350 (2012) 256–265.
Slide 50 - Molecular and Cellular Endocrinology 350 (2012) 256–265. MR, Aldosterone and Vascular Remodeling
Slide 51 - Mineralocorticoid receptors in vascular dysfunction and disease Molecular and Cellular Endocrinology 350 (2012) 256–265.
Slide 52 - MR and Myocardial Remodeling
Slide 53 - Cardiac tissue remodeling is characterised by: Accumulation of collagen fibers types I & III Cardiomyocyte hypertrophy Fibroblast proliferation Remodeling of the structural electrical coupling components of the myocardium MR, Aldosterone and Myocardial Remodeling Molecular and Cellular Endocrinology 350 (2012) 248–255.
Slide 54 - It is widely accepted that collagen synthesis is stimulated by a number of signaling molecules, including: Cytokines (IL-13, IL-21, TGF-b1) Chemokines (MCP-1 and MIP-1b) VEGF Osteopontin PAI-1 Endothelin-1 MR, Aldosterone and Myocardial Remodeling Molecular and Cellular Endocrinology 350 (2012) 248–255.
Slide 55 - Numerous studies have shown that, in the presence of a high salt diet, aldosterone increases interstitial and perivascular cardiac fibrosis. Conversely, aldosterone-infused rats on a low salt diet did not. The cardiac response to aldosterone is a direct, MR-dependent response, that is independent of the effect on blood pressure and the circulating and tissue RAS. MR, Aldosterone and Myocardial Remodeling Molecular and Cellular Endocrinology 350 (2012) 248–255.
Slide 56 - Aldosterone effect on the expression of profibrotic factors Clinical Science (2007) 113, 267–278.
Slide 57 - Macrophage MR are critical for the activation of tissue macrophages and the onset of fibrosis whereas vascular MR (endothelial cell and vascular smooth muscle cell, VSMC) and macrophage MR contribute to the increased systolic blood pressure response. Molecular and Cellular Endocrinology 350 (2012) 248–255.
Slide 58 - MR and Heart Failure
Slide 59 - Consistent with experimental studies, several clinical trials (RALES, EPHESUS, EMPHASIS-HF), have demonstrated a reduced mortality and morbidity when MR antagonists are included in the treatment of moderate–severe heart failure. The guidelines of American (ACC/AHA) and of the European (ESC) Societies of Cardiology recommend ACE inhibitors and beta-blockers as class I indication, then angiotensin receptor antagonists (ARBs) and MRAs. MR, Aldosterone and Heart Failure Molecular and Cellular Endocrinology 350 (2012) 266–272.
Slide 60 - ppt slide no 60 content not found
Slide 61 - Curr Heart Fail Rep (2011) 8:7–13. Characteristics of studies with MR antagonists
Slide 62 - Eur J Clin Invest 2012 DOI: 10.1111/j. 1365-2362.2012.02676.x
Slide 63 - Available evidence favors addition of MRA as the next step in heart failure on ACE inhibitor therapy rather than an ARB. In two recent meta-analyses, mortality was reduced by 25% (P=0.00001) with the addition of MRA vs. to no significance with added ARB. Thus, the data in aggregate (and cost) seem to favor the addition of MRAs over ARBs. However, despite the clear benefit of MRAs in several classes of HF they remain underused. MR, Aldosterone and Heart Failure Molecular and Cellular Endocrinology 350 (2012) 266–272.
Slide 64 - MR and Kidney Disease
Slide 65 - In 1996 a landmark study by Greene et al. reported that the protective effects of ACEI and ARB in renal ablation model are reversed by exogenous aldosterone infusion, clearly demonstrating that aldosterone plays a major role in causing kidney injury independent of angiotensin II. MR, Aldosterone and Chronic Kidney Disease Molecular and Cellular Endocrinology 350 (2012) 273–280.
Slide 66 - Previous studies have shown the presence of 11bHSD2 in the glomeruli and cultured podocytes, implying that aldosterone can directly modulate the glomerular cell function through MR. Aldosterone/salt-treated animals exhibit heavy proteinuria because of severe glomerular injury resulting in glomerulosclerosis. MR, Aldosterone and Chronic Kidney Disease Molecular and Cellular Endocrinology 350 (2012) 273–280.
Slide 67 - Almost all renal parenchyma are affected Vasculature Glomeruli Tubulointerstitium Renal vascular changes significantly contribute Transmural fibrinoid necrosis Intimal thickening Adventitial fibrosis MR, Aldosterone and Chronic Kidney Disease Molecular and Cellular Endocrinology 350 (2012) 273–280.
Slide 68 - Aldosterone causes glomerular injury, especially in podocytes that serve as the key filtration barrier in the glomeruli. Decreased glomerular expression of nephrin podocin Increased glomerular expression of desmin, a marker for podocyte damage In addition, these changes were almost completely prevented by the coadministration of eplerenone. MR, Aldosterone and Chronic Kidney Disease Molecular and Cellular Endocrinology 350 (2012) 273–280. Hypertension 2007;49:355–364.
Slide 69 - Involvement of podocyte damage in the renal dysfunction of aldosterone/salt-treated rats Hypertension 2007;49:355–364. 24h Urinary Protein
Slide 70 - Mechanisms of aldosterone/MR-induced kidney injury Molecular and Cellular Endocrinology 350 (2012) 273–280.
Slide 71 - Although hyperkalemia limits its use in renal insufficiency, accumulating data indicate that MR blockade can confer renoprotection. Clinical studies involving relatively small numbers of subjects reported that MR blockade effectively reduces proteinuria in subjects with hypertension, diabetes, and chronic kidney diseases. Other studies have shown that the combination of an ACEI with spironolactone decreases albuminuria more than the combination of an ACEI with an ARB. MR blockade and Chronic Kidney Disease Molecular and Cellular Endocrinology 350 (2012) 273–280.
Slide 72 - MR and the Metabolic Syndrome
Slide 73 - Plasma aldosterone in women correlated directly with visceral adipose tissue, and higher plasma aldosterone values have also been reported in patients with metabolic syndrome, which is independent of plasma renin activity. Accumulating studies have elucidated the close relationship between aldosterone and obesity. MR, Aldosterone and Metabolic Syndrome Molecular and Cellular Endocrinology 350 (2012) 273–280.
Slide 74 - The adipose tissue is an endocrine organ that secretes a variety of adipokines. Adipocytes are capable of stimulating adrenal aldosterone synthesis through the secretion of potent aldosterone-releasing factors (ARFs), which are not yet identified. Nonetheless, the adipose tissue does not express 11βHSD2, and MR in adipocytes are predominantly occupied by glucocorticoids which have an essential function in adipocytes. MR, Aldosterone and Metabolic Syndrome Molecular and Cellular Endocrinology 350 (2012) 273–280.
Slide 75 - Molecular and Cellular Endocrinology 350 (2012) 281–288. MR, Aldosterone and Metabolic Syndrome Aldosterone-releasing factors (ARFs)
Slide 76 - There is a worse control of BP in obese than lean hypertensives, which can also be related to excessive aldosterone. Aldosterone overproduction is an important cause of resistant hypertension and MR blockade has been shown to effectively reduce BP in such patients. MR, Aldosterone and Metabolic Syndrome Molecular and Cellular Endocrinology 350 (2012) 273–280.
Slide 77 - Adipocyte MR, Aldosterone and Metabolic Syndrome Hypertension 2010;55:813-818. type 1
Slide 78 - For 50 years aldosterone has been thought to act primarily on the renal epithelia to regulate fluid and electrolyte homeostasis. The discovery in the 1980s that aldosterone had a range of extrarenal MR receptors and actions, especially in the heart and blood vessels, has certainly renewed interest in the field of MR antagonists. Further studies will provide a clear understanding of the mechanisms of the MRAs beneficial effects in CV and Renal disease. Summary - MR and CardioRenal Disease Molecular and Cellular Endocrinology 350 (2012) 266–272.
Slide 79 - ΣΑΣ ΕΥΧΑΡΙΣΤΩ
Slide 80 - ppt slide no 80 content not found
Slide 81 - Molecular and Cellular Endocrinology 350 (2012) 273–280. Hypertension 2010;55:813-818. A hypothetical model of MR pathway activation in type 2 metabolic syndrome (no hyperaldosteronism) Metabolic syndrome type 2