Renin-Angiotensin System

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Editorial

Long Non-Coding RNA CCAT2 and Pathological Cardiac Remodeling

Gustavo Augusto Ferreira Mota et al. Mariana Gatto Claudia Maria Silva Cyrino Silvio Assis de Oliveira Júnior Marina Politi Okoshi

Despite advances in cardiovascular medicine, heart disease is a serious public health problem due to its high prevalence, elevated cost, and high morbidity and mortality. Therefore, it is necessary to improve the understanding of molecular mechanisms involved in the pathophysiology of cardiovascular disease.

Following cardiac injury, the heart undergoes a remodeling process, initially characterized by alterations in the genome expression. The changes lead to molecular, cellular, and interstitial modifications that manifest clinically as variations in the size, shape, and function of the heart. Cardiac remodeling is usually accompanied by activation of neurohormonal systems. Under physiological conditions, the renin-angiotensin system plays a fundamental role in regulating blood pressure and fluid-electrolyte balance. However, when excessively activated, it induces deleterious effects on the heart, such as myocyte hypertrophy and death and interstitial myocardial fibrosis.

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Research Letter

A “Grasp Heart” Situation: Managing Heart Failure with Reduced Ejection Fraction in Primary Adrenal Insufficiency

Matheo Augusto Morandi Stumpf et al. Madson Queiroz Almeida

Primary adrenal insufficiency (PAI) is a well-established risk factor for ischemic heart disease, the most prevalent cause of heart failure. Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and PAI is debatable. Here, we briefly discuss the evidence for treating both conditions.

Trials in this particular population are lacking in the literature. In 1983, a single prospective study showed a long-term follow-up of 22 patients with PAI. Seven patients developed HF during a mean follow-up of 30 years. Two of them did not receive mineralocorticoid replacement, while the remaining five had their fludrocortisone dose reduced (to a maximum of 0.1 mg/d). Three patients were advised to limit their sodium intake due to severe HF. HF was predominantly treated with digoxin and furosemide, the usual course of treatment at the time.

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Original Article

Improvement in Blood Pressure After Intermittent Fasting in Hipertension: Could Renin-Angiotensin System and Autonomic Nervous System Have a Role?

Erkan Demirci et al. Bekir Çalapkorur Oguzhan Celik Derya Koçer … Selami Demirelli Ziya Şimsek

Abstract

Background

Although it has been reported that the intermittent fasting (IF) diet has positive effects on heart health and improvement in blood pressure, it has not been sufficiently clarified how it could have these positive effects yet.

Objective

We aimed to evaluate the effects of IF on the autonomic nervous system (ANS) and renin-angiotensin system (RAS), which are closely related to blood pressure.

Methods

Seventy-two hypertensive patients were included in the study, and the data of 58 patients were used. All the participants fasted for about 15-16 hours for 30 days. Participants were evaluated with 24-hour ambulatory blood pressure monitoring and Holter electrocardiography before and after IF; also, 5 ml venous blood samples were taken for assessment of Serum angiotensin I (Ang-I) and angiotensin II (Ang-II) levels and angiotensin-converting enzyme (ACE) activity. For data analysis, the p-value <0.05 was accepted as significant.

Results

Compared to pre-IF, a significant decrease was observed in the patients’ blood pressures in post-IF. An increase in high-frequency (HF) power and the mean root square of the sum of squares of differences between adjacent NN intervals (RMSSD) were observed after the IF protocol (p=0.039, p=0.043). Ang-II and ACE activity were lower in patients after IF (p=0.034, p=0.004), and decreasing Ang-II levels were determined as predictive factors for improvement of the blood pressure, like the increase in HF power and RMSSD.

Conclusion

The present findings of our study demonstrated an improvement in blood pressure and the relationship of blood pressure with positive outcomes, including HRV, ACE activity, and Ang-II levels after the IF protocol.

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Viewpoint

A Probable Relationship between Physical Exercise and COVID-19 Mediated by the Renin-Angiotensin-Aldosterone System

Renato Aparecido de Souza et al. Priscila Missaki Nakamura Inaian Pignatti Teixeira Marco Tulio de Souza Wonder Passoni Higino

The Pathways of the RAAS

The classical pathway of the RAAS is initiated by the release of angiotensinogen by the liver, which, combined with renin secreted by the kidneys, produces angiotensin I (Angio I). Angio I is converted to angiotensin II (Angio II) by the action of the angiotensin-converting enzyme (ACE) in the lungs. The physiological effects of Angio II are mediated primarily through membrane receptors, especially of the Angio II type 1 (AT1) receptor. These receptors, when stimulated, promote vasoconstriction, hypertrophy and hyperplasia of vascular cells, sodium retention, generation of reactive oxygen species (ROS), and inflammatory, thrombotic and fibrotic processes, which can cause tissue damage.

A counter-regulatory pathway of the RAAS involves the conversion of Angio II to angiotensin 1–7 (Angio-1–7) and membrane receptors (MAS) through the enzymatic activity of angiotensin-converting enzyme 2 (ACE2), which promotes a vasodilatory, anti-inflammatory, anti-fibrotic, and anti-proliferative effect on the tissues. Under appropriate physiological conditions, there is a balance between these two RAAS pathways ().

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Editorial

Targeting the Renin-Angiotensin-Aldosterone System in Obesity

Ariane Vieira Scarlatelli Macedo

Short Editorial related to the article: AT₁Receptor Blockade Improves Myocardial Functional Performance in Obesity

Obesity has been increasing across the globe and markedly raising the prevalence of cardiovascular diseases (CVD). Obesity, particularly severe obesity, causes hemodynamic alterations that contribute to changing cardiac morphology, which may predispose to impaired ventricular function and heart failure. These alterations include a high cardiac output state in most cases, as well as left ventricular hypertrophy (LVH) and left ventricular (LV) diastolic dysfunction. Experimental studies and some investigations on humans propose that specific neurohormonal and metabolic alterations generally associated with obesity may lead to changes in cardiac structure and function.

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Editorial

Cardiac Fibrosis Occurs before Arterial Hypertension Becomes Well Defined?

Claudio Pinho

Target organ damage (TOD) of systemic arterial hypertension (AH) in the heart modifies the cardiomyocyte, Interstice and its arteries. Alterations that occur in AH include cardiomyocyte hypertrophy, connective tissue hyperplasia and neovascularization stimulation, among others.^– These alterations depend essentially on the stimulus of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS)^– which may not homogeneously impact Kidneys, heart, brain and blood vessels. The response of the connective tissue to AH induces collagen production by fibroblasts and consequently interstitial fibrosis.^–

Since 2006 with the data published by Das MK et al., we have started to correlate the presence of notches that form the fragmented QRS (fQRS) with non-homogeneous electrical conduction resulting from myocardial fibrosis which can be restorative or reactive.

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Original Article

Pericardial Parietal Mesothelial Cells: Source of the Angiotensin-Converting-Enzyme of the Bovine Pericardial Fluid

Ilsione Ribeiro de Sousa Filho et al. Isabela Cabral Cavicchioli Pereira Lourimar José de Morais Livia das Graças Vieito Lombardi Teodoro … Maria Laura Pinto Rodrigues Roseli Aparecida da Silva Gomes

Abstract

Background:

Angiotensin II (Ang II), the primary effector hormone of the renin-angiotensin system (RAS), acts systemically or locally, being produced by the action of angiotensin-converting-enzyme (ACE) on angiotensin I. Although several tissue RASs, such as cardiac RAS, have been described, little is known about the presence of an RAS in the pericardial fluid and its possible sources. Locally produced Ang II has paracrine and autocrine effects, inducing left ventricular hypertrophy, fibrosis, heart failure and cardiac dysfunction. Because of the difficulties inherent in human pericardial fluid collection, appropriate experimental models are useful to obtain data regarding the characteristics of the pericardial fluid and surrounding tissues.

Objectives:

To evidence the presence of constituents of the Ang II production paths in bovine pericardial fluid and parietal pericardium.

Methods:

Albumin-free crude extracts of bovine pericardial fluid, immunoprecipitated with anti-ACE antibody, were submitted to electrophoresis (SDS-PAGE) and gels stained with coomassie blue. Duplicates of gels were probed with anti-ACE antibody. In the pericardial membranes, ACE was detected by use of immunofluorescence.

Results:

Immunodetection on nitrocellulose membranes showed a 146-KDa ACE isoform in the bovine pericardial fluid. On the pericardial membrane sections, ACE was immunolocalized in the mesothelial layer.

Conclusions:

The ACE isoform in the bovine pericardial fluid and parietal pericardium should account at least partially for the production of Ang II in the pericardial space, and should be considered when assessing the cardiac RAS.

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Artigo Original

Heart failure treatment profile at the beta blockers era

Christiano Pereira Silva et al. Fernando Bacal Philippe Vieira Pires Sandrigo Mangini … Victor Sarli Issa Silvia Ferreira Ayub Moreira Paulo Roberto Chizzola Germano Emílio Conceição Souza Guilherme Veiga Guimarães Edimar Alcides Bocchi

OBJECTIVES: The inhibition of the rennin-angiotensin-aldosterone system (RAAS) and sympathetic autonomous nervous system has increased the perspective of survival in these patients, as well as allowing the improvement of the quality of life. The aim of this study was to evaluate the reality of the treatment employed and its impact on the disease in patients followed at a specialized heart failure (HF) outpatient clinic. METHODS: A sample of 96 patients followed at the HF and Transplant Outpatient Clinic of Heart Institute of the University of São Paulo School of Medicine (InCor -HCFMUSP) were evaluated. The data were collected during the ambulatory consultation from the medical files and through physical examination. Patients were randomly selected for the study. RESULTS: Most of the patients were Functional Class II (42.3%) and evolution stage C (94.9%). The medical prescription given to the patients was quite similar to the one recommended by the directives. Approximately 95% of them received RAAS inhibitors (ACE inhibitor – enalapril and captopril – or angiotensin receptor antagonist – losartan), whereas 85% of the patients additionally received beta blockers (carvedilol). The mean dose prescribed was also similar to the one used in large studies and reached more than 60% of the maximum dose for each medication. The hemodynamic data show that patients were stable, despite the intensity of the dysfunction and ventricular remodeling observed in these patients. CONCLUSION: Patients with HF followed by a specialized medical team receive a medical prescription that is closer to the recommended one. These patients, despite the marked characteristics of disease severity, achieve hemodynamic and clinical stability with an adequate therapeutic optimization.

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Original Article

Reduction in left ventricular hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enalapril and losartan

Antônio Carlos Avanza Jr et al. Lilian Mameri El Aouar José Geraldo Mill

OBJECTIVE: To compare the regression of left ventricular hypertrophy in patients with moderate hypertension treated with enalapril, losartan or a combination of the two drugs at lower doses. METHODS: Patients of both sexes with moderate hypertension confirmed by ambulatory monitoring of arte-rial blood pressure and with left ventricular hypertrophy on echocardiogram were assigned to three groups: enalapril (35 mg/day, n=15), losartan (175 mg/day, n=15) and enalapril+losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months. RESULTS: The three therapeutic regimens were equally effective in reducing blood pressure and left ventricular mass index (LVMI, g/m²): 141±3.9 to 123±3.6 in the enalapril group (p<0.05), from 147±3.8 to 133±2.8 in the losartan group (p<0.05), and from 146±3.0 to 116±4.0 in the enalapril+losartan group (p<0.05). However, the percent reduction of LVMI was significantly greater (p<0.01) in the enalapril+losartan group (20.5±5.0%) than in enalapril (12.4±3.2%) and the losartan (9.1±2.1%) groups. Normalization of LVMI was obtained in 10 out of the 16 patients who received enalapril+ losartan, in 6 out of the 15 patients who received only enalapril and in 4 out of the 15 patients treated with losartan. CONCLUSION: The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin.

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