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Renin-angiotensin-aldosterone system in insulin resistance and metabolic syndrome.

ABSTRACT: Obesity and its consequent complications such as hypertension and metabolic syndrome are increasing in incidence in almost all countries. Insulin resistance is common in obesity. Renin- angiotensin system (RAS) is an important target in the treatment of hypertension and drugs that act on RAS improve insulin resistance and decrease the incidence of type 2 diabetes mellitus, explaining the close association between hypertension and type 2 diabetes mellitus. RAS influences food intake by modulating the hypothalamic expression of neuropeptide Y and orexins via AMPK dephosphorylation. Estrogen reduces appetite by its action on the brain in a way similar to leptin, an anorexigenic action that seems to be mediated via hypothalamic pro-opiomelanocortin (POMC) neurons in the arcuate nucleus and synaptic plasticity in the arcuate nucleus similar to leptin. Estrogen stimulates lipoxin A4, a potent vasodilator and platelet anti-aggregator. Since both RAS and estrogen act on the hypothalamic neuropeptides and regulate food intake and obesity, it is likely that RAS modulates LXA4 synthesis. Thus, it is proposed that Angiotensin-II receptor blockers and angiotensin-converting enzymes and angiotensin-II antagonists may have the ability to augment LXA4 synthesis and thus bring about their beneficial actions.

SUBMITTER: Das UN

PROVIDER: S-EPMC5290902 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Renin-angiotensin-aldosterone system in insulin resistance and metabolic syndrome.

Das Undurti N UN

Journal of translational internal medicine 20160601 2

Obesity and its consequent complications such as hypertension and metabolic syndrome are increasing in incidence in almost all countries. Insulin resistance is common in obesity. Renin- angiotensin system (RAS) is an important target in the treatment of hypertension and drugs that act on RAS improve insulin resistance and decrease the incidence of type 2 diabetes mellitus, explaining the close association between hypertension and type 2 diabetes mellitus. RAS influences food intake by modulating ...[more]

PMID: 28191524

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Project description:RationalePatients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are up-regulated, but this may have long-term negative effects on the progression of iPAH.ObjectivesAssess systemic and pulmonary RAAS activity in patients with iPAH and determine the efficacy of chronic RAAS inhibition in experimental PAH.MethodsWe collected 79 blood samples from 58 patients with iPAH in the VU University Medical Center Amsterdam (between 2004 and 2010) to determine systemic RAAS activity.Measurements and main resultsWe observed increased levels of renin, angiotensin (Ang)I, and AngII, which were associated with disease progression (P < 0.05) and mortality (P < 0.05). To determine pulmonary RAAS activity, lung specimens were obtained from patients with iPAH (during lung transplantation, n = 13) and control subjects (during lobectomy or pneumonectomy for cancer, n = 14). Local RAAS activity in pulmonary arteries of patients with iPAH was increased, demonstrated by elevated angiotensin-converting enzyme activity in pulmonary endothelial cells and increased AngII type 1 (AT(1)) receptor expression and signaling. In addition, local RAAS up-regulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT(1) receptor signaling in patients with iPAH compared with control subjects. Finally, to determine the therapeutic potential of RAAS activity, we assessed the chronic effects of an AT(1) receptor antagonist (losartan) in the monocrotaline PAH rat model (60 mg/kg). Losartan delayed disease progression, decreased right ventricular afterload and pulmonary vascular remodeling, and restored right ventricular-arterial coupling in rats with PAH.ConclusionsSystemic and pulmonary RAAS activities are increased in patients with iPAH and are associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH.

Dataset Information

Renin-angiotensin-aldosterone system in insulin resistance and metabolic syndrome.

Publications

Renin-angiotensin-aldosterone system in insulin resistance and metabolic syndrome.

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