Enhancement of AT1 receptor-associated protein (ATRAP) in adipose tissue improves high fat diet (HFD)-induced visceral obesity and insulin resistance, and suppresses adipose oxidative stress. However, HFD loading is not a direct stimulatory factor for AT1 receptor. In the present study, we investigated the effect of chronic, low-dose angiotensin II (Ang II) stimulation on glucose and lipid metabolism in mice and functional role of ATRAP. ATRAP expression was higher in adipose tissue (5–10-fold) and skeletal muscle tissue (approximately 1.6-fold) in ATRAP transgenic (TG) mice compared with wild-type (WT) mice. After Ang II infusion, insulin sensitivity was impaired in WT mice, but this response was suppressed in TG mice. Unexpectedly, Ang II infusion did not affect the adipose tissue profile in WT or TG mice. However, in skeletal muscle tissue, Ang II stimulus caused an increase in oxidative stress and activation of p38 MAPK, resulting in a decrease in glucose transporter type 4 expression in WT mice. These responses were suppressed in TG mice. Our study suggests that Ang II-induced insulin resistance is suppressed by increased ATRAP expression in skeletal muscle tissue. Hyperactivity of AT1 receptor could be related to formation of insulin resistance related to metabolic syndrome.

Hypertension is highly prevalent worldwide and is one of the major risk factors for cardiovascular and renal diseases. Accumulated results of clinical trials showed that strict control of blood pressure (BP) is essential to prevent target organ damage and to reduce cardiovascular mortality in hypertensive patients. In many countries, major antihypertensive drugs are calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), angiotensinconverting enzyme (ACE) inhibitors, diuretics, and betablockers (including alpha/beta-blockers), according to the international hypertension guidelines (1-5).The vascular function parameters (arterial stiffness and central hemodynamics), including ankle-brachial pressure index (ABI), pulse wave velocity (PWV), cardio-ankle vascular index (CAVI), augmentation index (AI) and central systolic blood pressure (cSBP), do not always correlate with the peripheral brachial BP value, but do reflect the pressure load in the major organs. Several previous studies demonstrated that these variables (cSBP, AI, and PWV) are more closely related to organ damage than brachial BP (6-9). Previous meta-analyses also showed that the cSBP, AI, and PWV are independent risk factors for cardiovascular disease, and that these variables may reflect the different characteristics of the pathophysiologic abnormalities related to arterial stiffness (10,11). Therefore, it would be important to improve the vascular parameters of both arterial stiffness and central hemodynamics, in addition to reduction in the peripheral brachial BP value (clinic BP), for the efficient cardiovascular protection.Experimental and clinical evidence has reported that activation of the renin-angiotensin system (RAS) is involved in the pathogenesis of hypertension and the related target organ damage, and multiple studies have shown the usefulness of RAS blockade induced by ACE inhibitors and ARBs for the management of hypertension. In addition, several previous studies showed beneficial effects of the RAS inhibitors on the vascular function parameters (12-14). Furthermore, several preceding meta-analyses for effects of the RAS inhibitors on arterial stiffness and/or wave reflections also demonstrated the RAS inhibitors improved PWV and/or AI in certain pathological conditions (15,16). Interestingly, the system review and meta-analysis by Chen et al. in the recent issue of the Journal of Thoracic Disease (JTD) was conducted to analyze the clinical benefits of different antihypertensive agents in improving arterial stiffness in hypertensive patients (17). The effect of ARB on the improvement of the PWV was not superior to other types of antihypertensive agents, but ARB was superior to other types of antihypertensive agents for improving the AI in this system review and meta-analysis, thereby suggesting that ARB maybe superior to other antihypertensive agents to improve of arterial stiffness (17). The results of this systematic review and meta-analysis by Chen et al. would strengthen the clinical evidence in favor of ARB as one...