Antihypertensive effect and mechanism of Mytilus edulis-derived peptide in spontaneously hypertensive rats.

This study aimed to investigate the stability, hypotensive effects, and underlying mechanisms of Mytilus edulis-derived angiotensin-converting enzyme inhibitory peptides (MEPs-F) in spontaneously hypertensive rats (SHRs). The results demonstrated that MEPs-F exhibited remarkable stability under thermal treatment, various pH conditions, high-salt exposure, and simulated gastrointestinal digestion. The MEPs-F(H) group produced maximum short-term reductions of 49 mmHg in systolic blood pressure (SBP) and 71 mmHg in diastolic blood pressure (DBP), and the maximum long-term reductions reached 85 and 65 mmHg (SBP and DBP) compared to the SHR group. Moreover, MEPs-F-treated groups increased the level of the vasodilatory mediator nitric oxide (NO) and decreased the secretion of the potent vasoconstrictor endothelin-1 (ET-1), thereby rectifying the impaired NO/ET-1 equilibrium in SHRs. The antihypertensive mechanisms of MEPs-F were mediated through the dual modulation of the renin-angiotensin-aldosterone system (RAAS) and the TGF-β/Smad signaling pathway. Specifically, it reduced blood pressure (BP) by inhibiting the ACE/Ang II/AT1 axis and concurrently activating the ACE2/Ang-(1-7)/Mas axis. Additionally, MEPs-F suppressed the TGF-β/Smad pathway via downregulating the protein expression levels of TGF-β, Smad2, Smad3, and Smad4, and upregulating the protein expression level of Smad7. MEPs-F-treated groups decreased the Firmicutes/Bacteroidetes (F/B) ratio and significantly reduced the abundance of Lactobacillus in SHRs, ameliorating the gut microbiota dysbiosis associated with hypertension. This study highlighted MEPs-F's potential as a promising functional food component with multi-organ protective mechanisms in hypertension management.