AT1receptor antagonism attenuates target organ effects of salt excess in SHRs without affecting pressure

Our recent studies have demonstrated that salt excess in the spontaneously hypertensive rat (SHR) produces a modestly increased arterial pressure while promoting marked myocardial fibrosis and structural damage associated with altered coronary hemodynamics and ventricular function. The present study was designed to determine the efficacy of an angiotensin II type 1 (AT1) receptor blocker (ARB) in the prevention of pressure increase and development of target organ damage from high dietary salt intake. Eight-week-old SHRs were given an 8% salt diet for 8 wk; their age- and gender-matched controls received standard chow. Some of the salt-loaded rats were treated concomitantly with ARB (candesartan; 10 mg·kg−1·day−1). The ARB failed to reduce the salt-induced rise in pressure, whereas it significantly attenuated left ventricular (LV) remodeling (mass and wall thicknesses), myocardial fibrosis (hydroxyproline concentration and collagen volume fraction), and the development of LV diastolic dysfunction, as shown by longer isovolumic relaxation time, decreased ratio of peak velocity of early to late diastolic waves, and slower LV relaxation (minimum first derivative of pressure over time/maximal LV pressure). Without affecting the increased pulse pressure by high salt intake, the ARB prevented the salt-induced deterioration of coronary and renal hemodynamics but not the arterial stiffening or hypertrophy (pulse wave velocity and aortic mass index). Additionally, candesartan prevented the salt-induced increase in kidney mass index and proteinuria. In conclusion, the ARB given concomitantly with dietary salt excess ameliorated salt-related structural and functional cardiac and renal abnormalities in SHRs without reducing arterial pressure. These data clearly demonstrated that angiotensin II (via AT1receptors), at least in part, participated importantly in the pressure-independent effects of salt excess on target organ damage of hypertension.

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Prevalence, Biochemical and Clinical Characteristics of Resistant Hypertension

Revista de Chimie ◽

10.37358/rc.18.10.6637 ◽

2018 ◽

Vol 69 (10) ◽

pp. 2845-2849

Author(s):

Daniela Gurgus ◽

Elena Ardeleanu ◽

Carmen Gadau ◽

Roxana Folescu ◽

Ioan Tilea ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Resistant Hypertension ◽

Clinical Characteristics ◽

Salt Intake ◽

Target Organ Damage ◽

Multivariate Logistic Regression Analysis ◽

Organ Damage ◽

Left Ventricular ◽

High Salt Intake

The objectives of the present study were to evaluate the prevalence of resistant hypertension (RH) in primary care setting and to analyse its biochemical and clinical characteristics. After 3 months of treatment and evaluation, 721 (14.01%) of 5,146 patients with hypertension did not reach target office blood pressure of [ 140/90 mmHg. After exclusion of �white-coat effect� with ambulatory blood pressure, of secondary and pseudo- resistant hypertension, prevalence of RH was 6.74%. Lifestyle factors associated with RH were physical inactivity, obesity, high salt intake, smoking and excessive alcohol ingestion. Compared to controlled hypertension, RH patients presented higher incidence of family history of cardiovascular disease (38.90% vs 25.94%), diabetes mellitus (34.87% vs 19.01%), impaired fasting glucose (21.91% vs 19.07%), target organ damage (29.1% vs 15.95%), and cardiovascular disease (27.09% vs 17.06%). Dyslipidaemia (52.90% vs 42.03%), fasting plasma glucose (116.10�38.9 vs 107.80�37.2), HbA1c (6.41�1.42 vs 5.96�0.94), serum creatinine (1.09�0.27 vs 1.03�0.24) and microalbuminuria (21.90% vs 10.95%) were significantly higher in RH. Predictors of RH, determined by a multivariate logistic regression analysis were left ventricular hypertrophy (OD 2.14, 95% CI 1.32-3.69), renal impairment expressed as eGFR [ 60 ml/min/1.73m2 (OD 1.62, 95% CI 1.21-2.21) and the presence of cardiovascular disease (OD 1.48, 95% CI 1.02-2.16).

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Effects of inhibition of the renin-angiotensin system on hypertension-induced target organ damage: clinical and experimental evidence

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2021.1570 ◽

2021 ◽

Vol 91 (1) ◽

Author(s):

Maria Rosaria De Luca ◽

Daniela Sorriento ◽

Domenico Massa ◽

Valeria Valente ◽

Federica De Luise ◽

...

Keyword(s):

Angiotensin Ii ◽

Ace Inhibitors ◽

Ventricular Hypertrophy ◽

Target Organ Damage ◽

Renin Angiotensin System ◽

Organ Damage ◽

Left Ventricular ◽

Target Organ ◽

Angiotensin System ◽

Hypertensive Patients

The dysregulation of renin-angiotensin-system (RAS) plays a pivotal role in hypertension and in the development of the related target organ damage (TOD). The main goal of treating hypertension is represented by the long-term reduction of cardiovascular (CV) risk. RAS inhibition either by angiotensin converting enzyme (ACE)-inhibitors or by type 1 Angiotensin II receptors blockers (ARBs), reduce the incidence of CV events in hypertensive patients. Actually, ACE-inhibitors and ARBs have been demonstrated to be effective to prevent, or delay TOD like left ventricular hypertrophy, chronic kidney disease, and atherosclerosis. The beneficial effects of RAS blockers on clinical outcome of hypertensive patients are due to the key role of angiotensin II in the pathogenesis of TOD. In particular, Angiotensin II through an inflammatory-mediated mechanism plays a role in the initiation, progression and vulnerability of atherosclerotic plaque. In addition, Angiotensin II can be considered the hormonal transductor of the pressure overload in cardiac myocytes, and through an autocrine-paracrine mechanism plays a role in the development of left ventricular hypertrophy. Angiotensin II by modulating the redox status and the immune system participates to the development of chronic kidney disease. The RAS blocker should be considered the first therapeutic option in patients with hypertension, even if ACE-inhibitors and ARBs have different impact on CV prevention. ARBs seem to have greater neuro-protective effects, while ACE-inhibitors have greater cardio-protective action.

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Mapping and confirmation of a major left ventricular mass QTL on rat chromosome 1 by contrasting SHRSP and F344 rats

Physiological Genomics ◽

10.1152/physiolgenomics.00067.2013 ◽

2013 ◽

Vol 45 (18) ◽

pp. 827-833 ◽

Cited By ~ 1

Author(s):

Katja Grabowski ◽

Gerold Koplin ◽

Bujar Aliu ◽

Leonard Schulte ◽

Angela Schulz ◽

...

Keyword(s):

Salt Intake ◽

Target Organ Damage ◽

Left Ventricular ◽

High Salt ◽

Chromosome 1 ◽

Dietary Salt ◽

A Genome ◽

High Salt Intake ◽

Lv Mass ◽

Major Qtl

An abnormal increase in left ventricular (LV) mass, i.e., LV hypertrophy (LVH), represents an important target organ damage in arterial hypertension and has been associated with poor clinical outcome. Genetic factors are contributing to variation in LV mass in addition to blood pressure and other factors such as dietary salt intake. We set out to map quantitative trait loci (QTL) for LV mass by comparing the spontaneously hypertensive stroke-prone (SHRSP) rat with LVH and normotensive Fischer rats (F344) with contrasting low LV mass. To this end we performed a genome-wide QTL mapping analysis in 232 F2 animals derived from SHRSP and F344 exposed to high-salt (4% in chow) intake for 8 wk. We mapped one major QTL for LV mass on rat chromosome 1 (RNO1) that demonstrated strong linkage (peak logarithm of odds score 8.4) to relative LV weight (RLVW) and accounted for ∼19% of the variance of this phenotype in F2 rats. We therefore generated a consomic SHRSP-1F344 strain in which RNO1 from F344 was introgressed into the SHRSP background. Consomic and SHRSP animals showed similar blood pressures during conventional intra-arterial measurements, while RLVW was already significantly lower (−17.7%, P < 0.05) in SHRSP-1F344 in response to a normal-salt diet; a similar significant reduction of LV mass was also observed in consomic rats after high-salt intake ( P < 0.05 vs. SHRSP). Thus, a major QTL on RNO1 was confirmed with significant impact on LV mass in the hypertensive background of SHRSP.

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Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism

Hormone and Metabolic Research ◽

10.1055/a-1116-2407 ◽

2020 ◽

Vol 52 (06) ◽

pp. 386-393

Author(s):

Christian Adolf ◽

Holger Schneider ◽

Daniel A. Heinrich ◽

Laura Handgriff ◽

Martin Reincke

Keyword(s):

Cardiovascular Risk ◽

Primary Aldosteronism ◽

Salt Intake ◽

Target Organ Damage ◽

Organ Damage ◽

Target Organ ◽

World Health ◽

Salt Appetite ◽

Dietary Salt ◽

Dietary Salt Intake

AbstractFirst described in 1955 by Jerome W. Conn, primary aldosteronism (PA) today is well established as a relevant cause of secondary hypertension and accounts for about 5–10 % of hypertensives. The importance of considering PA is based on its deleterious target organ damage far beyond the effect of elevated blood pressure and on PA being a potentially curable form of hypertension. Aside the established contributory role of high dietary salt intake to arterial hypertension and cardiovascular disease, high salt intake is mandatory for aldosterone-mediated deleterious effects on target-organ damage in patients with primary aldosteronism. Consequently, counselling patients on the need to reduce salt intake represents a major component in the treatment of PA to minimize cardiovascular damage. Unfortunately, in PA patients salt intake is high and far beyond the target values of 5 g per day, recommended by the World Health Organization. Insufficient patient motivation for lifestyle interventions can be further complicated by enhancing effects of aldosterone on salt appetite, via central and gustatory pathways. In this context, treatment for PA by adrenalectomy results in a spontaneous decrease in dietary salt intake and might therefore provide further reduction of cardiovascular risk in PA than specific medical treatment alone. Furthermore, there is evidence from clinical studies that even after sufficient treatment of PA dietary salt intake remains a relevant prognostic factor for cardiovascular risk. This review will focus on the synergistic benefits derived from both blockade of aldosterone-mediated effects and reduction in dietary salt intake on cardiovascular risk.

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Correlation among high salt intake, blood pressure variability, and target organ damage in patients with essential hypertension

Medicine ◽

10.1097/md.0000000000019548 ◽

2020 ◽

Vol 99 (14) ◽

pp. e19548

Author(s):

Wei Cai ◽

MingJian Lang ◽

XiaoBo Jiang ◽

Qian Yu ◽

Congliang Zhou ◽

...

Keyword(s):

Blood Pressure ◽

Essential Hypertension ◽

Blood Pressure Variability ◽

Salt Intake ◽

Target Organ Damage ◽

Organ Damage ◽

Target Organ ◽

High Salt ◽

High Salt Intake

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High Salt Intake Is Independently Associated With Hypertensive Target Organ Damage

Journal of Clinical Hypertension ◽

10.1111/jch.12668 ◽

2015 ◽

Vol 18 (4) ◽

pp. 315-321 ◽

Cited By ~ 12

Author(s):

Yuki Imaizumi ◽

Kazuo Eguchi ◽

Takeshi Murakami ◽

Kimika Arakawa ◽

Takuya Tsuchihashi ◽

...

Keyword(s):

Salt Intake ◽

Target Organ Damage ◽

Organ Damage ◽

Target Organ ◽

High Salt ◽

High Salt Intake

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High salt intake is associated with target organ damage independently of BP

Journal of the American Society of Hypertension ◽

10.1016/j.jash.2015.03.189 ◽

2015 ◽

Vol 9 (4) ◽

pp. e80

Author(s):

Yuki Imaizumi ◽

Kazuo Eguchi ◽

Takuya Tsuchihashi ◽

Kazuomi Kario

Keyword(s):

Salt Intake ◽

Target Organ Damage ◽

Organ Damage ◽

Target Organ ◽

High Salt ◽

High Salt Intake

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Effects of irbesartan on phenotypic alterations in monocytes and the inflammatory status of hypertensive patients with left ventricular hypertrophy

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02004-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jingsi Zhang ◽

Lina Yang ◽

Yanchun Ding

Keyword(s):

Ventricular Hypertrophy ◽

Target Organ Damage ◽

Organ Damage ◽

Left Ventricular ◽

Target Organ ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Hypertensive Patients ◽

Inflammatory Status ◽

Tnf Α

Abstract Background Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension and the resulting target organ damage. In this study, we observed alterations in the monocyte phenotype and inflammatory state of hypertensive patients with left ventricular hypertrophy (LVH) and studied the effects of irbesartan in these patients. This study might reveal a novel mechanism by which irbesartan alleviates LVH, and it could provide new targets for the prevention and treatment of hypertensive target organ damage. Methods CD163 and CD206 expression on monocytes and IL-10 and TNF-α levels in the serum of hypertensive patients with or without LVH and of healthy volunteers were detected. Furthermore, we treated monocytes from the LVH group with different concentrations of irbesartan, and then, CD163, CD206, IL-10 and TNF-α expression was detected. Results We found, for the first time, that the expression of CD163, CD206 and IL-10 in the LVH group was lower than that in the non-LVH group and healthy control group, but the TNF-α level in the LVH group was significantly higher. Irbesartan upregulated the expression of CD163 and CD206 in hypertensive patients with LVH in a concentration-dependent manner. Irbesartan also increased the expression of IL-10 and inhibited the expression of TNF-α in monocyte culture supernatants in a concentration-dependent manner. Conclusions Our data suggest that inflammation was activated in hypertensive patients with LVH and that the monocyte phenotype was mainly proinflammatory. The expression of proinflammatory factors increased while the expression of anti-inflammatory factors decreased. Irbesartan could alter the monocyte phenotype and inflammatory status in hypertensive patients with LVH. This previously unknown mechanism may explain how irbesartan alleviates LVH. Trail registration The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Dalian Medical University. Each patient signed the informed consent form.

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