The adipose-tissue renin–angiotensin–aldosterone system: role in the metabolic syndrome?

Engeli, Stefan; Schling, Petra; Gorzelniak, Kerstin; Boschmann, Michael; Janke, Jürgen; Ailhaud, Gérard; Teboul, Michèle; Massiéra, Florence; Sharma, Arya M.

doi:10.1016/s1357-2725(02)00311-4

Cited by 368 publications

(335 citation statements)

References 123 publications

Supporting

Mentioning

312

Contrasting

Unclassified

Order By: Relevance

“…15 Aliskiren may therefore offer treatment benefits compared with ARBs for BP reduction in patients with hypertension and metabolic syndrome or obesity-perhaps because of its distribution to adipose tissue, as adipocytes may contribute to BP elevation in obesity-related hypertension through the generation of Ang II. 5,25 More studies are required to investigate further the effects of aliskiren in patients with hypertension and metabolic disorders.…”

Section: Discussionmentioning

confidence: 99%

“…3 Chronic activation of the renin-angiotensin-aldosterone system (RAAS) is implicated in many of the key features of metabolic syndrome, including hypertension, insulin resistance and abdominal obesity. [4][5][6] Human adipocytes express mRNA and protein of many components of the RAAS, including angiotensinogen, angiotensinconverting enzyme and angiotensin receptors. 7 The local generation and release of angiotensin II (Ang II) by adipose tissue may therefore contribute to hypertension and can also influence adipocytokine secretion, thereby having a potential role in the development of features of the metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…7 The local generation and release of angiotensin II (Ang II) by adipose tissue may therefore contribute to hypertension and can also influence adipocytokine secretion, thereby having a potential role in the development of features of the metabolic syndrome. 5 Guidelines from the European Society of Hypertension recommend that RAAS inhibition with angiotensin-converting enzyme inhibitors should be preferred over calcium channel blockers, b-blockers and thiazide diuretics for anti-hypertensive therapy in patients with metabolic syndrome. 8 However, despite current anti-hypertensive treatment approaches, patients with obesity and metabolic syndrome still have greater difficulty achieving BP control compared with patients with hypertension who do not have these additional risk factors.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

Krone

Hanefeld

Hf³

et al. 2010

J Hum Hypertens

View full text Add to dashboard Cite

Metabolic syndrome, a cluster of risk factors that increase the risk of cardiovascular morbidity and mortality, is common in patients with hypertension. Chronic renin-angiotensin-aldosterone system (RAAS) activation, shown by elevated plasma renin activity (PRA), is implicated in many of the features of metabolic syndrome. The direct renin inhibitor aliskiren may be of benefit in this patient group as aliskiren targets the RAAS at the rate-limiting step. In this double-blind study, 141 patients with hypertension (mean baseline BP 155/93 mm Hg) and metabolic syndrome (modified National Cholesterol Education Program ATP III criteria) were randomized to aliskiren 300 mg or irbesartan 300 mg once daily. Patients treated with aliskiren 300 mg had their mean sitting blood pressure (BP) lowered by 13.8/ 7.1 mm Hg after 12 weeks, significantly greater (Pp0.001) than the 5.8/2.8 mm Hg reduction observed in patients treated with irbesartan 300 mg. A significantly greater proportion of patients treated with aliskiren achieved BP control to o135/85 mm Hg (29.2 vs 16.7% with irbesartan; P ¼ 0.019). Aliskiren treatment led to a 60% decrease in PRA from baseline, whereas irbesartan increased PRA by 99% (both Po0.001). Aliskiren and irbesartan had similar effects on glucose and lipid profiles and on a panel of biomarkers of inflammation and cardiovascular risk. Both aliskiren and irbesartan were well tolerated. Collectively, these results suggest that aliskiren 300 mg may offer treatment benefits compared with irbesartan 300 mg for BP reduction in patients with hypertension and metabolic syndrome.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

Krone

Hanefeld

Hf³

et al. 2010

J Hum Hypertens

View full text Add to dashboard Cite

show abstract

“…All components of RAS are evident in adipocytes, but their contribution to hypertension and metabolic disease is still uncertain. 39,40 Further, different levels of expression of RAS components are evident in subcutaneous vs visceral adipose tissue. 41 Other peptide hormones secreted by adipose tissue include leptin, adipsin, plasminogen activator inhibitor-1 (PAI-1), adiponectin, and resistin, and their regulation is altered when fat mass is markedly altered.…”

Section: Discussionmentioning

confidence: 99%

Hydralazine as antihypertensive therapy in obesity-related hypertension

2004

View full text Add to dashboard Cite

OBJECTIVE:The objectives were two-fold: (1) determine whether the use of hydralazine as antihypertensive therapy during obesity development exacerbated obesity-related cardioacceleration and hormonal abnormalities; (2) determine whether the absence of hypertension in obesity attenuated obesity-related abnormalities in hemodynamics, cardiac hypertrophy, and hormonal profile. DESIGN: Female New Zealand White rabbits were divided into lean control (n ¼ 12), lean hydralazine-treated (n ¼ 9), obese control (n ¼ 11), and obese hydralazine-treated (n ¼ 8) groups. Pretreatment mean blood pressure (BP) and heart rate (HR) were determined using telemetry. Pretreatment BP was maintained during 12 weeks of obesity development using hydralazine. MEASUREMENTS: Chronically measured BP and HR; plasma/blood volume; wet and dry ventricular weights; body fat/water; and hormonal profile (plasma renin activity, aldosterone, cortisol, atrial natriuretic peptide, adrenaline, and noradrenaline). RESULTS: Hydralazine treatment in obese animals attenuated obesity-related renin-angiotensin system (RAS) activation. In contrast, RAS was activated in lean hydralazine, as indicated by increased plasma aldosterone. The absence of hypertension in obese hydralazine did not result in attenuation of cardioacceleration, cardiac hypertrophy, or intravascular volumes. CONCLUSIONS: Hydralazine treatment in obese rabbits did not exacerbate obesity-related cardiovascular and hormonal alterations. Cardioacceleration and cardiac hypertrophy persisted in obese hydralazine despite BP control, suggesting hypertension-independent effects of obesity on these variables. Hydralazine's effects on RAS activation differed in lean and obese rabbits, suggesting that the systemic effects of hydralazine as a control therapy in evaluation of antihypertensive medications may differ depending on the underlying pathology.

show abstract

“…38 Indeed, adipocytes can produce and release angiotensinogen and may have the complete enzymatic machinery for local production of angiotensin II. 39 Furthermore, abdominal visceral fat has been shown to express more angiotensinogen than does subcutaneous fat. 40 However, it is not known whether perivascular adipocytes can release angiotensinogen or angiotensin II in significant amounts to diffuse to and affect neighboring VSMC.…”

Section: Ectopic Fat Storage In the Heartmentioning

confidence: 99%

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

et al. 2004

View full text Add to dashboard Cite

In humans and most animal models, the development of obesity leads not only to increased fat depots in classical adipose tissue locations but also to significant lipid deposits within and around other tissues and organs, a phenomenon known as ectopic fat storage. The purpose of this review is to explore the possible locations of ectopic fat in key target-organs of cardiovascular control (heart, blood vessels and kidneys) and to propose how ectopic fat storage can play a role in the pathogenesis of cardiovascular diseases associated with obesity. In animals fed a high-fat diet, cardiac fat depots within and around the heart impair both systolic and diastolic functions, and may in the long-term promote heart failure. Accumulation of fat around blood vessels (perivascular fat) may affect vascular function in a paracrine manner, as perivascular fat cells secrete vascular relaxing factors, proatherogenic cytokines and smooth muscle cell growth factors. Furthermore, high amounts of perivascular fat could mechanically contribute to the increased vascular stiffness seen in obesity. Finally, accumulation of fat in the renal sinus may limit the outflow of blood and lymph from the kidney, which would alter intrarenal physical forces and promote sodium reabsorption and arterial hypertension. Taken together, ectopic fat storage in key target-organs of cardiovascular control may impair their functions, contributing to the increased prevalence of cardiovascular diseases in obese subjects.

show abstract

The adipose-tissue renin–angiotensin–aldosterone system: role in the metabolic syndrome?

Cited by 368 publications

References 123 publications

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

Comparative efficacy and safety of aliskiren and irbesartan in patients with hypertension and metabolic syndrome

Hydralazine as antihypertensive therapy in obesity-related hypertension

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

Contact Info

Product

Resources

About