RESUMO
BACKGROUND: Phlegm-dampness constitution is a traditional Chinese medicine constitution typically associated with essential hypertension. Previous studies have demonstrated that auricular acupuncture effectively decreases blood pressure and adjusts the constitution. However, the mechanism underlying auricular acupuncture's effect is poorly understood. METHODS: A non-blinded, randomized controlled trial will be undertaken between September 2022 and May 2023. Eighty essential hypertensive patients with a phlegm-dampness constitution will be randomly allocated to one of two groups. The intervention group will receive eight weeks of auricular acupuncture and regular use of antihypertensive drugs, while the control group will only receive antihypertensive drugs. The primary outcome will be any mean differences in office systolic blood pressure. The secondary outcomes investigations will include proteins of the renin-angiotensin system, office blood pressure of different genotypes, and phlegm-dampness constitution scores. DISCUSSION: By demonstrating how auricular acupuncture affects the renin-angiotensin system, this research will offer significant new information on the mechanism underlying the action of auricular acupuncture in hypertension. Moreover, the results will provide crucial clinical information on the associations between renin-angiotensin system gene polymorphisms and the antihypertensive effects of auricular acupuncture. TRIAL REGISTRATION: Registered at the chictr.org.
Assuntos
Terapia por Acupuntura , Acupuntura Auricular , Hipertensão , Humanos , Pressão Sanguínea , Anti-Hipertensivos , Sistema Renina-Angiotensina , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Consuming a highsodium diet carries serious health risks and significantly influences the activation state of the renin-angiotensin system (RAS). This study evaluates the protective effect of angiotensin-converting enzyme (ACE) inhibitory peptide IVGFPAYGH on a highsodium diet-induced liver injury. IVGFPAYGH supplementation increased the activities of liver antioxidase and decreased the levels of liver inflammatory factor in mice fed a highsodium diet (8 % NaCl). IVGFPAYGH supplementation also reduced liver fatty acid synthesis and promoted fatty acid oxidation, increased the expression of low-density lipoprotein receptor, and improved liver dyslipidemia. Furthermore, IVGFPAYGH supplementation inhibited the activation of the liver RAS via inhibiting ACE activity and reducing angiotensin II levels in mice fed a highsodium diet. Moreover, IVGFPAYGH supplementation could alter the gut microbiota composition toward a normal gut microbiota composition and increase the abundance of the Lactobacillus genus. IVGFPAYGH supplementation also increased the expression levels of small intestinal tight junction protein and cecum short-chain fatty acids. Thus, IVGFPAYGH supplementation may maintain intestinal homeostasis and improve highsodium diet-induced liver injury by altering the gut microbiota composition and inhibiting the RAS. IVGFPAYGH is a promising functional ingredient for protecting liver damage caused by a highsodium diet.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Camundongos , Animais , Sistema Renina-Angiotensina/fisiologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Angiotensina II/metabolismo , Ácidos Graxos/metabolismo , Sódio/metabolismo , Dieta , Dieta Hiperlipídica , Camundongos Endogâmicos C57BLRESUMO
Diabetic kidney disease (DKD) is a serious complication of diabetes and is the primary cause of end-stage renal disease. Current treatment strategies primarily focus on the inhibition of the renin-angiotensin-aldosterone system and the attainment of blood glucose control. Although current medical therapies for DKD have been shown to delay disease progression and improve long-term outcomes, their efficacy is limited and they may be restricted in certain cases, particularly when hyperkalemia is present. Traditional Chinese medicine (TCM) treatment has emerged as a significant complementary approach for DKD. TCM monomers, derived from various Chinese herbs, have been found to modulate multiple therapeutic targets and exhibit a broad range of therapeutic effects in patients with DKD. This review aims to summarize the mechanisms of action of TCM monomers in the treatment of DKD, based on findings from clinical trials, as well as cell and animal studies. The results of these investigations demonstrate the potential effective use of TCM monomers in treating or preventing DKD, offering a promising new direction for future research in the field. By providing a comprehensive overview of the mechanisms and efficacy of TCM monomers in DKD, this review highlights the potential of these natural compounds as alternative therapeutic options for improving outcomes in patients with DKD.
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Diabetes Mellitus , Nefropatias Diabéticas , Falência Renal Crônica , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Sistema Renina-AngiotensinaRESUMO
Advancements in biological sciences revealed the significant role of angiotensin-converting enzyme 2 (ACE2), a key cell surface receptor in various human pathologies. ACE2 is a metalloproteinase that not only functions in the regulation of Angiotensin II but also possesses some non-catalytic roles in the human body. There is considerable uncertainty regarding its protein expression, despite its presence in virtually all organs. The level of ACE2 expression and its subcellular localisation in humans may be a key determinant of susceptibility to various infections, symptoms, and outcomes of numerous diseases. Therefore, we summarize the distribution and expression pattern of ACE2 in different cell types related to all major human tissues and organs. Moreover, this review constitutes accumulated evidences of the important resources for further studies on ACE2 Inhibitory capacity via different natural compounds in order to understand its mechanism as the potential drug target in disease pathophysiology and to aid in the development of an effective therapeutic approach towards the various diseases.
Assuntos
Peptidil Dipeptidase A , Sistema Renina-Angiotensina , Humanos , Peptidil Dipeptidase A/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Angiotensina II/metabolismoRESUMO
Hypertension is a serious concern as it is one of the causes of kideny failure and pulmonary fibrosis. An important therapeutic strategy for treating chronic hypertension is to inhibit the angiotensin converting enzyme (ACE). ACE inhibition reduces kidney damage, pulmonary artery pressure, and high blood pressure. Due to their high efficacy and low risk of side effects, natural renin-angiotensin system inhibitors have drawn increasing attention over the past decades. Alkaloids, amino acids, anthocyanidins, flavonoids, glucosinolates, isoflavonoids, phenolic acids, polyphenolics, and triterpenoids are among the bioactive metabolites pocessing an impressive ACE inhibitory activity. Many herbs including Rosmarinus officinalis, Hibiscus sabdariffa, Curcuma longa, Rauwolfia serpentina, Emblica officinalis, Cynara scolymus, Punica granatum, Mucuna pruriens, Capsicum annuum, and Moringa olifera were found having ACE inhibitory activities comparable to captopril and enalpril. These enticing natural ACE inhibitors deserve to be a safeguard medicine against hypertension, respiratory distress syndrome, and chronic kidney diseases. More clinical trials are required before new natural compounds and herbs can be used to treat chronic hypertension and its ramifications, such as respiratory distress syndrome and kidney failure.
Assuntos
Hipertensão , Insuficiência Renal Crônica , Síndrome do Desconforto Respiratório , Humanos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Sistema Renina-Angiotensina , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológicoRESUMO
Diabetes is the most frequent cause of kidney disease that progresses to end-stage renal disease worldwide, and diabetic kidney disease is significantly related to unfavorable cardiovascular outcomes. Since the 1990s, specific therapies have emerged and been approved to slow the progression of diabetic kidney disease, namely, renin-angiotensin-aldosterone system blockers (including angiotensin-converting enzyme inhibitors (ACEi) angiotensin receptor blockers (ARBs), the non-steroidal mineralocorticoid receptor antagonist (NS-MRA), finerenone, and sodium-glucose cotransporter-2 (SGLT2) inhibitors). Mechanistically, these different classes of agents bring different anti-inflammatory, anti-fibrotic, and complementary hemodynamic effects to patients with diabetic kidney disease such that they have additive benefits on slowing disease progression. Within the coming year, there will be data on renal outcomes using the glucagon-like peptide-1 receptor agonist, semaglutide. All the aforementioned medications have also been shown to improve cardiovascular outcomes. Thus, all three classes (maximally dosed ACEi or ARB, low-dose SGLT-2 inhibitors, and the NS-MRA, finerenone) form the "pillars of therapy" such that, when used together, they maximally slow diabetic kidney disease progression. Ongoing studies aim to expand these pillars with additional medications to potentially normalize the decline in kidney function and reduce associated cardiovascular mortality.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Falência Renal Crônica , Humanos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Sistema Renina-Angiotensina , Falência Renal Crônica/etiologia , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Diabetes Mellitus/tratamento farmacológicoRESUMO
The role of taurine in the treatment of congestive heart failure (CHF) in dogs without systemic deficiency is unexplored. Taurine might have beneficial cardiac effects aside from deficit replacement. We hypothesized that oral taurine supplementation administered to dogs with naturally-occurring CHF would suppress the renin-angiotensin aldosterone system (RAAS). Oral taurine was administered to 14 dogs with stable CHF. Serum biochemical variables, blood taurine concentrations, and comprehensive analysis of RAAS variables were compared before and 2 weeks after taurine supplementation added to background furosemide and pimobendan therapy for CHF. Whole blood taurine concentrations increased after supplementation (median 408 nMol/mL, range 248-608 before and median 493 nMol/mL, range 396-690 after; P = .006). Aldosterone to angiotensin II ratio (AA2) was significantly decreased after taurine supplementation (median 1.00, range 0.03-7.05 before and median 0.65, range 0.01-3.63 after; P = .009), but no other RAAS components significantly differed between timepoints. A subset of dogs showed marked decreases in RAAS metabolites after supplementation and these dogs were more likely to have been recently hospitalized for CHF treatment than dogs that did not show marked decreases in classical RAAS metabolites. Overall, taurine only lowered AA2 in this group of dogs, however, response heterogeneity was noted, with some dogs showing RAAS suppression.
Assuntos
Insuficiência Cardíaca , Sistema Renina-Angiotensina , Cães , Animais , Aldosterona/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Furosemida , Suplementos NutricionaisRESUMO
The regulation of plasma glucose levels is a complex and multifactorial process involving a network of receptors and signaling pathways across numerous organs that act in concert to ensure homeostasis. However, much about the mechanisms and pathways by which the brain regulates glycemic homeostasis remains poorly understood. Understanding the precise mechanisms and circuits employed by the central nervous system to control glucose is critical to resolving the diabetes epidemic. The hypothalamus, a key integrative center within the central nervous system, has recently emerged as a critical site in the regulation of glucose homeostasis. Here, we review the current understanding of the role of the hypothalamus in regulating glucose homeostasis, with an emphasis on the paraventricular nucleus, the arcuate nucleus, the ventromedial hypothalamus, and lateral hypothalamus. In particular, we highlight the emerging role of the brain renin-angiotensin system in the hypothalamus in regulating energy expenditure and metabolic rate, as well as its potential importance in the regulation of glucose homeostasis.
Assuntos
Hipotálamo , Sistema Renina-Angiotensina , Encéfalo/metabolismo , Metabolismo Energético/fisiologia , Glucose/metabolismo , Homeostase/fisiologia , Hipotálamo/metabolismo , Humanos , AnimaisRESUMO
BACKGROUND: Astragalus root is a commonly used herb in traditional Chinese medicine. Although renoprotective effects have been reported in some clinical and experimental studies, the details remain unknown. METHODS: We used 5/6 nephrectomized rats as chronic kidney disease (CKD) models. At 10 weeks, they were divided into four groups, namely, CKD, low-dose astragalus (AR400), high-dose astragalus (AR800), and sham groups. At 14 weeks, they were sacrificed for the evaluation of blood, urine, mRNA expression in the kidney, and renal histopathology. RESULTS: Kidney dysfunction was significantly improved following astragalus administration (creatinine clearance: sham group; 3.8 ± 0.3 mL/min, CKD group; 1.5 ± 0.1 mL/min, AR400 group; 2.5 ± 0.3 mL/min, AR800 group; 2.7 ± 0.1 mL/min). Blood pressure, urinary albumin, and urinary NGAL levels were significantly lower in the astragalus-treated groups than those in the CKD group. Excretion of urinary 8-OHdG, an oxidative stress marker, and intrarenal oxidative stress were lower in the astragalus-treated groups than those in the CKD group. Furthermore, the mRNA expression of NADPH p22 phox, NADPH p47 phox, Nox4, renin, angiotensin II type 1 receptor, and angiotensinogen in the kidney was lower in the astragalus-treated groups compared with the CKD group. CONCLUSION: This study suggests that astragalus root slowed CKD progression, possibly through the suppression of oxidative stress and the renin-angiotensin system.
Assuntos
Rim , Insuficiência Renal Crônica , Ratos , Animais , NADP/metabolismo , NADP/farmacologia , NADP/uso terapêutico , Rim/patologia , Renina , Sistema Renina-Angiotensina , RNA Mensageiro/metabolismoRESUMO
Hypertension is the third leading cause of the global disease burden, and while populations live longer, adopt more sedentary lifestyles, and become less economically concerned, the prevalence of hypertension is expected to increase. Pathologically elevated blood pressure (BP) is the strongest risk factor for cardiovascular disease (CVD) and related disability, thus making it imperative to treat this disease. Effective standard pharmacological treatments, i.e., diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocker (ARBs), beta-adrenergic receptor blockers (BARBs), and calcium channel blockers (CCBs), are available. Vitamin D (vitD) is known best for its role in bone and mineral homeostasis. Studies with vitamin D receptor (VDR) knockout mice show an increased renin-angiotensin-aldosterone system (RAAS) activity and increased hypertension, suggesting a key role for vitD as a potential antihypertensive agent. Similar studies in humans displayed ambiguous and mixed results. No direct antihypertensive effect was shown, nor a significant impact on the human RAAS. Interestingly, human studies supplementing vitD with other antihypertensive agents reported more promising results. VitD is considered a safe supplement, proposing its great potential as antihypertensive supplement. The aim of this review is to examine the current knowledge about vitD and its role in the treatment of hypertension.
Assuntos
Anti-Hipertensivos , Conservadores da Densidade Óssea , Hipertensão , Vitamina D , Animais , Humanos , Camundongos , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/terapia , Sistema Renina-Angiotensina , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Receptores de Calcitriol/genética , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêuticoRESUMO
BACKGROUND: Membranous nephropathy (MN) is one of the cardinal causes of nephrotic syndrome in adults, but an adequate treatment regimen is lacking. PURPOSE: We assessed the effect of Moshen granule (MSG) on patients with MN and cationic bovine serum albumin (CBSA)-induced rats. We further identified the bioactive components of MSG and revealed the underlying molecular mechanism of its renoprotective effects. METHODS: We determined the effect of MSG on patients with MN and CBSA-induced rats and its components on podocyte injury in zymosan-activated serum (ZAS)-elicited podocytes and revealed their regulatory mechanism on the Wnt/ß-catenin/renin-angiotensin system (RAS) signalling axis. RESULTS: MSG treatment improved renal function and reduced proteinuria in MN patients and significantly reduced proteinuria and preserved the protein expression of podocin, nephrin, podocalyxin and synaptopodin in CBSA-induced MN rats. Mechanistically, MSG treatment significantly inhibited the protein expression of angiotensinogen, angiotensin converting enzyme and angiotensin II type 1 receptor, which was accompanied by inhibition of the protein expression of Wnt1 and ß-catenin and its downstream gene products, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in CBSA-induced MN rats. We further identified 81 compounds, including astragaloside IV (AGS), calycosin, barleriside A and geniposidic acid, that preserve the podocyte-specific protein expression in ZAS-induced podocytes. Among these four compounds, AGS exhibited the strongest inhibitory effects on podocyte protein expression. AGS treatment significantly inhibited the protein expression of RAS components and Wnt1 and ß-catenin and its downstream gene products in ZAS-induced podocytes. In contrast, the inhibitory effect of AGS on podocyte-specific proteins, ß-catenin downstream gene products and RAS components was partially abolished in ZAS-induced podocytes treated with ICG-001 and ß-catenin siRNA. CONCLUSION: This study first demonstrates that AGS mitigates podocyte injury by inhibiting the activation of RAS signalling via the Wnt1/ß-catenin pathway by both pharmacological and genetic methods. Therefore, AGS might be considered a new ß-catenin inhibitor that inhibits the Wnt1/ß-catenin pathway to retard MN in patients.
Assuntos
Glomerulonefrite Membranosa , Sistema Renina-Angiotensina , Ratos , Animais , beta Catenina/metabolismo , Proteinúria , Via de Sinalização WntRESUMO
BACKGROUND: Many patients with indications for renin-angiotensin-aldosterone system inhibitor (RAASi) therapy are not receiving these medications. Concern about hyperkalemia is thought to contribute to this lack of evidence-based therapy. METHODS: A retrospective cohort study included adult patients in primary care practices affiliated with an integrated health care delivery system treated with RAASi between 2000 and 2019 for any of the following indications: (a) coronary artery disease (CAD); (b) heart failure (HF) with a left ventricle ejection fraction ≤ 40%; (c) diabetes mellitus (DM) with proteinuria; or (d) chronic kidney disease (CKD) with proteinuria. Relationship between hyperkalemia (K > 5.0 mEg/L) over the first 12 months of follow-up and a composite end point of cardiovascular events, renal dysfunction, and all-cause mortality was evaluated. RESULTS: Among 82,732 study patients, 7,727 (9.34%) developed hyperkalemia. Patients with hyperkalemia were older (69.0 vs 64.6) and more likely to have CAD (57.8 vs 53.7%), CKD (57.3 vs 51.1%), HF (19.3 vs 9.7%), and DM (45.3 vs 33.3%) (P < .001 for all). Five-year cumulative risk of the primary outcome was higher in patients who did (63.9%; 95% CI: 62.8%-65.1%) versus did not (37.2%; 95% CI: 36.8%-37.6%) develop hyperkalemia. Five-year cumulative risk of ED visit or hospitalization for hyperkalemia was 15.6% (14.7%-16.6%) for patients with versus 2.7% (95% CI: 2.6-2.9) for patients without hyperkalemia, rising to 25.9% (95% CI: 22.4-29.9) for patients with severe (K > 6.0 mEq/dL) hyperkalemia. Patients who experienced hyperkalemia were more likely (34.4%) than patients who did not (29.2%) to deintensify RAASi therapy (P < .001). Five-year cumulative risk of the primary outcome was higher in patients who lowered RAASi dose (50.4%; 95% CI: 48.5%-52.4%) or stopped RAASi therapy completely (49.3%; 95% CI: 48.5%-50.1%), compared to patients who continued RAASi therapy (36.1%; 95% CI: 25.7-36.5). Similar findings were observed in multivariable analyses and for individual components of the primary outcome. CONCLUSIONS: Hyperkalemia is a common complication of RAASi therapy and is associated with an increased risk of multiple adverse outcomes. Patients who have their RAASi medications deintensified after a hyperkalemic event have higher incidence of cardiovascular events, renal dysfunction and death.
Assuntos
Doença da Artéria Coronariana , Insuficiência Cardíaca , Hiperpotassemia , Insuficiência Renal Crônica , Adulto , Humanos , Sistema Renina-Angiotensina , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Aldosterona , Estudos Retrospectivos , Anti-Hipertensivos/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , Doença da Artéria Coronariana/complicações , Proteinúria/induzido quimicamente , Proteinúria/complicações , Proteinúria/tratamento farmacológico , PotássioRESUMO
Background: Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Methods: Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. Results: HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Conclusions: Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.
Assuntos
Diabetes Mellitus Experimental , Extratos Vegetais , Securidaca , Animais , Masculino , Ratos , Angiotensina II , Citocinas/metabolismo , Modelos Animais , Pâncreas , Extratos Vegetais/farmacologia , Ratos Wistar , Sistema Renina-Angiotensina , Securidaca/química , Sementes/química , Estreptozocina , Diabetes Mellitus Experimental/metabolismoRESUMO
Atherosclerosis, a chronic inflammatory disease of the arteries that appears to have been as prevalent in ancient as in modern civilizations, is predisposing to life-threatening and life-ending cardiac and vascular complications, such as myocardial and cerebral infarctions. The pathogenesis of atherosclerosis involves intima plaque buildup caused by vascular endothelial dysfunction, cholesterol deposition, smooth muscle proliferation, inflammatory cell infiltration and connective tissue accumulation. Hypertension is an independent and controllable risk factor for atherosclerotic cardiovascular disease (CVD). Conversely, atherosclerosis hardens the arterial wall and raises arterial blood pressure. Many CVD patients experience both atherosclerosis and hypertension and are prescribed medications to concurrently mitigate the two disease conditions. A substantial number of publications document that many pathophysiological changes caused by atherosclerosis and hypertension occur in a manner dependent upon circadian clocks or clock gene products. This article reviews progress in the research of circadian regulation of vascular cell function, inflammation, hemostasis and atherothrombosis. In particular, it delineates the relationship of circadian organization with signal transduction and activation of the renin-angiotensin-aldosterone system as well as disturbance of the sleep/wake circadian rhythm, as exemplified by shift work, metabolic syndromes and obstructive sleep apnea (OSA), as promoters and mechanisms of atherogenesis and risk for non-fatal and fatal CVD outcomes. This article additionally updates advances in the clinical management of key biological processes of atherosclerosis to optimally achieve suppression of atherogenesis through chronotherapeutic control of atherogenic/hypertensive pathological sequelae.
Assuntos
Aterosclerose , Ritmo Circadiano , Humanos , Animais , Aterosclerose/complicações , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Genômica , Túnica Íntima/patologia , Sistema Renina-Angiotensina , Hipertensão/patologia , Fatores de Risco de Doenças CardíacasRESUMO
Coronavirus disease (COVID-19) is an infectious disease caused by a new virus that causes respiratory illness. Older adults and individuals who have pre-existing chronic medical conditions are at higher risk for more serious complications from COVID-19. Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, cardiovascular events and associated comorbidities, which are the main causes of severe clinical complications in COVID-19 patients. Considering the defensive role of vitamin D, mediated through modulation of the innate and adaptive immune system as well as inhibition of the Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.
Assuntos
COVID-19 , Vitamina D , Humanos , Idoso , COVID-19/complicações , Peptidil Dipeptidase A , SARS-CoV-2/metabolismo , Sistema Renina-Angiotensina , Vitaminas/uso terapêuticoRESUMO
BACKGROUND: Renin and angiotensin system inhibitors (RAASi) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended for patients with diabetic kidney disease (DKD) to reduce the progression to end-stage kidney disease; however, they are under-prescribed. OBJECTIVE: To evaluate the frequency of care gaps in RAASi and SGLT2i prescription by patient demographic, health system, and clinical factors in patients with DKD. DESIGN: Retrospective cohort study. PARTICIPANTS: Adult primary care patients with DKD at an integrated health system in Bronx, NY, with 23 primary care sites in 2021. MAIN MEASURES: The odds of having a care gap for (1) SGLT2i or (2) RAASi prescription. Multivariate logistic regression models were performed for each outcome measure to evaluate associations with patient demographic, health system, and clinical factors. KEY RESULTS: Of 7199 patients with DKD, 80.3% had a care gap in SGLT2i prescription and 42.0% had a care gap in RAASi prescription. For SGLT2i, patients with A1C at goal (aOR 2.32, 95% CI 1.96-2.73), Black non-Hispanic race/ethnicity (aOR 1.46, 95% CI 1.15-1.87), and Hispanic race/ethnicity (aOR 1.46, 95% CI 1.11-1.92) were more likely to experience a care gap. For RAASi, patients with blood pressure at goal (aOR 1.34, 95% CI 1.21-1.49) were more likely to experience a care gap. CONCLUSIONS: The care gaps for SGLT2i and RAASi for patients with DKD with well-controlled diabetes and blood pressure suggest failure to recognize DKD as an independent indication for these medications. Racial/ethnic disparities for SGLT2i, but not for RAASi, suggest systemic racism exacerbates care gaps for novel medications. These factors can be targets for interventions to improve patient care.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Prescrições , Glucose , SódioRESUMO
Adverse changes in cardiovascular and renal systems are major contributors to overall morbidity and mortality. Human cardiovascular and renal systems exhibit a complex network of positive and negative feedback that is reflected in the control of vascular tone via angiotensin II (Ang II) based signaling. This review will examine in some depth, the multiple components and processes that control the status and reflect the health of these various cardiovascular and renal systems, such as pathways associated to monomeric G proteins, RhoA/Rho kinase system and ERK, oxidative stress and NO balance. It will specifically emphasize the "yin-yang" nature of Ang II signaling by comparing and contrasting the effects and activity of various systems, pathways and components found in hypertension to those found in Gitelman's and Bartter's syndromes (GS/BS), two rare autosomal recessive tubulopathies characterized by electrolytic imbalance, metabolic alkalosis, sodium wasting and prominent activation of the renin-angiotensin-aldosterone system. Notwithstanding the activation of the renin-angiotensin-aldosterone system, GS/BS are normo-hypotensive and protected from cardiovascular-renal remodeling and therefore can be considered the mirror image, the opposite of hypertension.
Assuntos
Angiotensina II , Hipertensão , Humanos , Rim , Sistema Renina-Angiotensina , CaquexiaRESUMO
This study aimed to identify the no-observed-adverse-effect level (NOAEL) of dietary epigallocatechin gallate (EGCG) supplementation and its possible antihypertensive and nutrigenomics effects in modulating intrarenal renin-angiotensin system (RAS) gene expression in spontaneously hypertensive rats (SHR). EGCG (50, 250, 500 or 1000 mg/kg b.w. i.g., once daily) was administered to SHR for 28 days. All the SHR survived with no signs of systemic toxicity. Increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and thiobarbituric acid reactive substances (TBARS) were evident in SHR supplemented with 500 and 1000 mg/kg b.w. but not in those supplemented with lower doses of EGCG. Subsequently, the NOAEL of EGCG was established at 250 mg/kg b.w., and the same protocol was replicated to assess its effects on blood pressure and renal RAS-related genes in SHR. The systolic blood pressure (SBP) of the EGCG group was consistently lower than the control group. The mRNA levels of cortical Agtr2 and Ace2 and medullary Agtr2, Ace and Mas1 were upregulated while medullary Ren was downregulated in EGCG group. Statistical analysis showed that SBP reduction was associated with the changes in medullary Agtr2, Ace, and Ren. Dietary EGCG supplementation exhibits antihypertensive and nutrigenomics effects through activation of intrarenal Ace and Agtr2 and suppression of Ren mediators, while a high dose of EGCG induced liver damage in SHR. In future clinical studies, liver damage biomarkers should be closely monitored to further establish the safety of the long-term use of EGCG.
Assuntos
Hipertensão , Sistema Renina-Angiotensina , Ratos , Animais , Ratos Endogâmicos SHR , Anti-Hipertensivos/farmacologia , Hipertensão/metabolismo , Pressão Sanguínea , Suplementos NutricionaisRESUMO
One of the major complications of diabetes mellitus (DM) is diabetic cardiomyopathy (DCM) due to the multifaceted therapy involved. Here, we evaluated the combinatorial effect of Moringa leaf (ML) and seed (MS) supplemented diets plus acarbose (ACA) on cardiac acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), adenosine deaminase (ADA), monoamine oxidase (MAO), arginase, angiotensin-I converting enzyme (ACE), and lactate dehydrogenase (LDH) activities, thiobarbituric acid reactive species (TBARS), and thiols levels. The diets and ACA (25 mg/kg) were administered for 14 days. The fasting blood glucose level (FBGL), cardiac AChE, ATPase, ADA, MAO, arginase, ACE, LDH activities, and TBARS and thiol levels were determined. Relative to the normal rats, the biomarkers were significantly increased in DM rats but were suppressed significantly in the diets plus ACA-treated rats while improving antioxidant status, with the 4% Moringa plus ACA proving outstanding compared to individual ML/MS and ACA. In addition, ML-supplemented diets with/without ACA had better effects compared to MS with/without ACA, respectively. In conclusion, the combination of ML/MS supplemented diets and ACA synergistically modulates the tested biochemicals. However, the effect on blood vessels and the nerves that control the heart, stiffness of left ventricular (LV) hypertrophy, fibrosis, cell signaling abnormalities, related gene expression, clinical trials, and echocardiology studies should be further investigated to affirm this claim. PRACTICAL APPLICATIONS: Moringa oleifera has been a vocal appetite in mitigating cardiovascular disease induced by diabetes, but the formulation of a medicinal diet as an ameliorative route of attention to the pathology is fairly addressed, not talking of its combination with the synthetic antidiabetic drug, such as ACA. Based on this experiment, it is imperative to explore such an idea. This research shows that co-administration of moringa leaf/seed formulated diets plus ACA exhibits a synergistic effect in DCM management. However, further research is needed in this field of experiment.
Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Suplementos Nutricionais , Moringa , Animais , Ratos , Acarbose/uso terapêutico , Acetilcolinesterase/metabolismo , Adenosina Trifosfatases/metabolismo , Antioxidantes/metabolismo , Arginase , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/complicações , Cardiomiopatias Diabéticas/patologia , Dieta , Monoaminoxidase/metabolismo , Moringa/química , Ratos Wistar , Sistema Renina-Angiotensina , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin 'antipeptides'. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite effects at AR1 receptors. Agonism and inverse agonism at AR1 receptors can be explained by a receptor 'switching' between an activated state invoking receptor dimerization/G protein coupling and an inverse agonist state mediated by an alternative/second messenger that is slow to reverse. Both receptor states appear to be driven by the formation of the ANG II charge-relay system involving TyrOH-His/imidazole-Carboxylate (analogous to serine proteases). In this system, tyrosinate species formed are essential for activating AT1 and AT2 receptors. ANGII is also known to bind to the zinc-coordinated metalloprotease angiotensin converting enzyme 2 (ACE2) used by the COVID-19 virus to enter cells. Here we report in silico results demonstrating the binding of a new class of anionic biphenyl-tetrazole sartans ('Bisartans') to the active site zinc atom of the endopeptidase Neprilysin (NEP) involved in regulating hypertension, by modulating humoral levels of beneficial vasoactive peptides in the RAS such as vasodilator angiotensin (1-7). In vivo and modeling evidence further suggest Bisartans can inhibit ANG II-induced pulmonary edema and may be useful in combatting SARS-CoV-2 infection by inhibiting ACE2-mediated viral entry to cells.