Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: An integrated view in humans

Department of Internal Medicine, Centre for Atherosclerosis and Metabolic Syndrome (Hypertension Excellence Centre of the European Society of Hypertension), University of Ancona - Politecnica delle Marche, Ancona, Italy.
Journal of Hypertension (Impact Factor: 4.72). 06/2008; 26(5):831-43. DOI: 10.1097/HJH.0b013e3282f624a0
Source: PubMed


The obesity pandemic is closely related to hypertension and metabolic syndrome. Visceral adipose tissue plays a key role in the metabolic and cardiovascular complications of being overweight. The pathophysiological link between visceral adiposity and cardiometabolic complications focuses on insulin sensitivity, sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS) and, only recently, on cardiac natriuretic peptide system (CNPS). RAAS and CNPS are endogenous antagonistic systems on sodium balance, cardiovascular system, and metabolism. The circulating RAAS is dysregulated in obese patients, and adipose tissue has a full local renin-angiotensin system that is active at local and systemic level. Adipocyte biology and metabolism are influenced by local renin-angiotensin system, with angiotensin II acting as a 'growth factor' for adipocytes. CNPS induces natriuresis and diuresis, reduces blood pressure, and, moreover, has powerful lipolytic and lipomobilizing activity in humans but not in rodents. In obesity, lower plasmatic natriuretic peptides levels with increasing BMI, waist circumference, and metabolic syndrome have been documented. Thus, reduced CNPS effects coupled with increased RAAS activity have a central role in obesity and its deadly complications. We propose herein an integrated view of the dysregulation of these two antagonistic systems in human obesity complicated with hypertension, metabolic syndrome, and increased cardiovascular risk.

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    • "Osteoporosis may have some elements of a lipotoxic disease in which marrow fat affects the cellular components of bone remodeling, formation, and resorption. BNP is a potent lipolytic agent that acts in adipose tissue via the BNP-cyclic guanosine monophosphateedependent protein kinase signal transduction cascade, which increases fat oxidation [10] [30]. "
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    ABSTRACT: Bone mineral density (BMD) was significantly lower in heart failure patients. Our aim was to evaluate the relationship between BMD and fasting serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in renal transplant recipients. Fasting blood samples were obtained from 69 renal transplant recipients. BMD was measured by dual energy x-ray absorptiometry in lumbar vertebrae (L2-L4). Serum NT-proBNP levels were measured by electrochemiluminescence immunoassay. Among the renal transplant recipients, 8 patients (11.6%) had osteoporosis and 28 (40.6%) had osteopenia; 33 had a normal BMD. Increased serum NT-proBNP (P < .001) and decreased body mass index (P = .033) and body weight (P = .010) were significantly correlated with low lumbar T-score cutoff points between groups (normal, osteopenia, and osteoporosis). Women had lower lumbar BMD than did men (P = .013). Menopause in women (P = .005), use of tacrolimus (P = .020), and use of cyclosporine (P = .046) among renal transplant recipients were associated with lower lumbar BMD. Multivariate forward stepwise linear regression analysis of the significant variables revealed that log-transformed NT-proBNP (β, -0.545; R(2) = 0.331; P < .001), and body weight (β, 0.273, R(2) = 0.104; P = .005) were independent predictors of lumbar BMD values among the renal transplant recipients. Serum NT-proBNP concentrations correlate negatively with lumbar BMD values among renal transplant recipients and may be an alternative to energy x-ray absorptiometry for identifying at risk of osteoporosis in renal transplant recipients. Copyright © 2014 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 12/2014; 46(10):3443-7. DOI:10.1016/j.transproceed.2014.06.077 · 0.98 Impact Factor
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    • "Besides nutritional and metabolic factors, hemodynamic alterations, and vascular dysfunction are believed to play a role (Mather et al. 2013). Vasomotor peptide systems, especially the renin–angiotensin and kallikrein–kinin systems (KKS), have been suggested to be involved in the development of insulin resistance (Mayfield et al. 1996, Sarzani et al. 2008), a hypothesis that has been recently supported by the results of clinical trials. "
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    ABSTRACT: The kallikrein kinin system has been suggested to participate in control of glucose metabolism. Its role and the role of angiotensin I converting enzyme, major kinin-inactivating enzyme, are however debated. We have evaluated the consequence of deficiency in tissue kallikrein (TK), the main kinin-forming enzyme, on development of insulin resistance and diabetes in mouse and man.Mice with inactivation of the tissue kallikrein gene were fed high-fat diet for 3 months, or crossed with obese, leptin deficient (ob/ob) mice to generate double ob/ob-TK deficient mutants. In man, a loss-of-function polymorphism of the tissue kallikrein gene (R53H) was studied in a large general population cohort tested for insulin resistance, the D.E.S.I.R study (4,843 participants, 9 year follow-up).Mice deficient in tissue kallikrein gained less weight on high-fat diet than wild-type littermates. Fasting glucose level was increased and responses to glucose (GTT) and insulin (ITT) tolerance tests were altered at 10 and 16 weeks of high-fat diet compared to standard diet but tissue kallikrein deficiency had no influence on these parameters. Likewise, ob-TK-/- mice had similar GTT and ITT responses compared to ob-TK+/+ mice. Tissue kallikrein deficiency had no effect on blood pressure in both models. In humans, changes over time in body mass index, fasting plasma glucose, insulinemia, and blood pressure were not influenced by the defective 53H-coding tissue kallikrein allele. Incidence of diabetes was not influenced by this allele.These data do not support a role for tissue kallikrein-kinin system, protective or deleterious, in development of insulin resistance and diabetes.
    Journal of Endocrinology 03/2014; 221(2). DOI:10.1530/JOE-13-0529 · 3.72 Impact Factor
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    • "The renin-angiotensin-aldosterone system is activated in obese patients and angiotensin II acting as a ‘growth factor’ for adipose tissue growth and development [4]. BNP binds its common receptor, guanylyl cyclase-A (GC-A), which leads to biological actions through a cyclic guanosine monophosphate (cGMP)-dependent pathway and has an inhibition effect of the renin–angiotensin–aldosterone axis [2]. "
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    ABSTRACT: Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) was lower in the general population with metabolic syndrome (MetS). The aim of this study was to evaluate the relationship between MetS and fasting serum NT-proBNP concentration in elderly persons. Fasting blood samples were obtained from 84 elderly volunteers aged 65 years or older. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Thirty-eight elderly persons (45.2%) had MetS. Fasting NT-proBNP level was negatively correlated with MetS among elderly patients (p = 0.001). Univariate linear regression analysis showed that age (r = 0.338; p = 0.002) was positively correlated with fasting serum log-NT-proBNP levels, while height (r = -0.253; p = 0.020), body weight (r = -0.238; p = 0.029), waist circumference (r = -0.270; p = 0.013), body fat mass (r = -0.356; p = 0.002) and triglyceride (r = -0.291; p = 0.007) were negatively correlated with fasting serum log-NT-proBNP levels among the elderly persons. Multivariate forward stepwise linear regression analysis of the significant variables showed that age (R2 change = 0.114, p = 0.011), triglyceride (R2 change = 0.118, p < 0.001), body fat mass (R2 change = 0.084, p < 0.001), and height (R2 change = 0.101, p < 0.001) were the independent predictor of fasting serum log-NT-proBNP levels in elderly persons. NT-proBNP level is significantly reduced in elderly persons affected by MetS, and is significantly positively related to age, while negatively related to triglyceride, body fat mass, height in these subjects.
    Diabetology and Metabolic Syndrome 02/2014; 6(1):15. DOI:10.1186/1758-5996-6-15 · 2.17 Impact Factor
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