IRW peptide (Ile-Arg-Trp) 10 mg (Without mannitol)

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Hypertension, affecting approximately 25% of adults globally, is a pivotal risk factor for cardiovascular diseases. In 2017, its definition shifted from 140/90 mmHg to 130/80 mmHg for systolic/diastolic blood pressure, leading to a higher incidence as per the American Heart Association (AHA) and the American College of Cardiology (ACC). Essential hypertension, accounting for 95% of cases, is a complex condition influenced by various factors. One major aspect is an overactive renin angiotensin system (RAS), pivotal in blood pressure regulation. Angiotensin II (Ang II), a vasoconstrictor in RAS, plays a significant role in vascular structure and function. Excessive Ang II levels lead to vascular cell abnormalities, oxidative stress, and inflammation, promoting vascular remodeling and increased resistance, a key factor in essential hypertension. Inhibiting Ang II generation via ACE inhibition is a common strategy for hypertension therapy.

In 2000, angiotensin-converting enzyme 2 (ACE2) emerged, sharing homology with ACE but exerting opposite effects. ACE2 counters Ang II’s harmful actions by converting it to angiotensin (1‐7) (Ang (1‐7)), which mitigates Ang II effects through the mas receptor (MasR). Elevated ACE2 levels have shown positive effects on cardiovascular functions in animal models mimicking human hypertension. ACE2 overexpression in spontaneously hypertensive rats (SHRs) reduced blood pressure, oxidative stress, and cardiac remodeling. ACE2 supplementation countered Ang II-induced hypertrophy, underscoring its beneficial cardiovascular effects and presenting ACE2 as a novel therapeutic target for hypertension.

Given the side effects of long-term use of antihypertensive drugs, interest has surged in food protein-derived antihypertensive peptides as a safer alternative. While most identified antihypertensive peptides act as ACE inhibitors, those targeting ACE2 are scarcely reported. Our lab previously identified an antihypertensive peptide, Ile‐Arg‐Trp (IRW), from egg white ovotransferrin, demonstrating blood pressure-lowering effects in SHRs. Molecular investigations revealed IRW’s impact on intracellular vascular cell events and its role in reducing SHRs’ blood pressure. Intriguingly, IRW administration upregulated ACE2 mRNA in the mesenteric artery and activated both in vitro ACE2 and cellular ACE2 activities. Moreover, oral IRW administration increased ACE2 protein expression in the aorta and kidney of SHRs, indicating its potential as an ACE2 activator. However, the direct link between IRW-induced ACE2 activation and reduced blood pressure remains unexplored.

This study hypothesizes that IRW activates the ACE2/Ang (1‐7)/MasR axis, potentially contributing to blood pressure reduction in SHRs.