Therapeutic Potential of Big-Belly Seahorse Derived Peptide in Blood Pressure Regulation and Protection Against Aortic, Renal, and Cardiac Injuries on Spontaneously Hypertensive Rats

<b>Background/Objectives:</b> Marine-derived bioactive peptides have been reported to possess blood pressure-regulatory effects. However, most studies have focused on the antihypertensive effects after single-dose administration, and research on long-term administration and its protective effects against hypertension-induced tissue damage remains limited. Therefore, this study aimed to investigate the long-term antihypertensive efficacy of IGTGIPGIW, a bioactive peptide derived from <i>Hippocampus abdominalis</i> (<i>H. abdominalis</i>), and its protective effects on hypertension-related tissue damage. <b>Methods:</b> To evaluate the blood pressure-regulatory effects, spontaneously hypertensive rats (SHRs) were orally administered a high-dose (50 mg/kg) IGTGIPGIW peptide group (H-IGTGIPGIW) for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were monitored weekly. Serum levels of angiotensin II (Ang II), angiotensin-converting enzyme (ACE), and angiotensin-converting enzyme 2 (ACE2) were measured to assess the peptide's regulatory effects on the renin-angiotensin system. Histological analyses of the aorta and heart tissues were performed to evaluate the protective effects against hypertension-induced tissue damage. <b>Results:</b> After 8 weeks of treatment, H-IGTGIPGIW significantly reduced SBP, DBP, and MAP compared with SHRs. Serum Ang II and ACE levels were significantly decreased, while ACE2 levels were significantly increased. Histological analyses demonstrated that IGTGIPGIW alleviated aortic wall thickening and reduced renal and cardiac tissue damage in SHR. <b>Conclusions:</b> IGTGIPGIW, a bioactive peptide derived from <i>H. abdominalis</i>, effectively regulated blood pressure by modulating serum Ang II, ACE, and ACE2 levels. Moreover, it protected against hypertension-induced aortic, renal and cardiac tissue damage, suggesting its potential as a functional ingredient for managing hypertension.