Angiotensin receptor blocker ameliorates hypertension, improves glucose intolerance, and reduces visceral fat in OLETF rats fed a high-cholesterol diet

Metabolic Syndrome (MetS) affects more than 30% of the US population and unmanaged can lead to cardiovascular disease and type II diabetes mellitus. MetS is a cluster of conditions, which include elevated arterial pressure, poor glucose tolerance with or without insulin resistance, and abdominal obesity. Existing literature has demonstrated high cholesterol diet’s (HCD) potential to develop MetS cluster factor conditions like dyslipidemia. Our lab has previously shown that angiotensin receptor blockers (ARBs), a common therapy to treat hypertension by disrupting the renin-angiotensin-aldosterone system (RAAS), attenuate cluster factor conditions of MetS. However, the efficacy of ARBs during the consumption of a HCD remains unclear. Otsuka Long Evan Tokushima Fatty (OLETF) rats (a MetS model) were fed an HCD and at presentation of elevated arterial pressure, they were treated with ARB (10 mg olmesartan/kg/d x 3 wks) by oral gavage. Blood pressure was monitored in real-time with surgically implanted radio telemeters. ARB reduced systolic blood pressure by 15±1mmHg (11%; p<0.05). ARB also reduced BM by 3% (p<0.05) in chow-fed and 4% (p<0.05) in HCD-fed OLETF compared to OLETF. However, there was no difference in BM between OLETF+ARB and OLETF+HCD+ARB. Neither, HCD nor ARB alone reduced abdominal fat in OLETF rats. Although, ARB in OLETF+HCD induced visceral fat loss (37%; p<0.05) compared to OLETF. Additionally, ARB reduced AUCglucose by 28% (P<0.05) and tended to reduce fasting blood glucose by 19% (p=0.06). These findings demonstrate that chronic treatment of ARB can effectively ameliorate MetS-associated hypertension, hyperglycemia, and abdominal obesity despite the additional insult of a HCD. This work was supported by the National Institutes of Health NCMHD 9T37MD001480 and National Institutes of Health, National Center on Minority Health and Health Disparities. E.E.J was supported by NIH GRISE BIO-STeP. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.