This study aimed to investigate whether hydrolyzed collagen (HC) derived from salmon skin could attenuate blood pressure and vascular damage in Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Hypertension was induced in rats by the oral administration of L-NAME (40 mg/kg/day) for eight weeks, while HC in two doses (50, 450 mg/kg) or enalapril at 10 mg/kg dissolved in water were concurrently administered via oral gavage for the last four weeks. Treatment with HC (450 mg/kg) and enalapril resulted in a reduction in systolic blood pressure, oxidative stress markers, and inflammatory cytokines. Production of serum nitric oxide (NO) was also increased, contributing to better aortic function. Histopathological analysis confirmed these changes, showing enhanced progression in the aorta structure. Vascular function was improved, as evidenced by significantly higher relaxation responses to acetylcholine (ACh) in the presence or absence of endothelium. These findings indicate that HC effectively lowered the blood pressure in hypertensive rats, potentially through mechanisms involving the modulation of oxidative stress and the expression of nitric oxide, reducing vascular inflammation and remodeling, hence enhancing vascular function.

Hydrolyzed collagen (HC) derived from salmon skin is a promising source of bioactive peptides. In this study, the vasorelaxant effects and potential mechanisms of action of HC on isolated rat thoracic aorta rings were investigated using the organ bath technique. The vasorelaxant properties of HC were evaluated using aortic rings from Wistar rats pre-contracted with phenylephrine (PE) or potassium chloride (KCl). HC induced significant vasorelaxation in both endothelium-intact and endothelium-denuded rings, indicating that its mechanism of action was independent of the endothelium and involved direct effects on vascular smooth muscle cells. The vasorelaxant effect of HC was reduced when pre-contraction was induced by tetraethylammonium chloride (TEA). However, the vasodilatory effects of HC were not significantly inhibited by all K⁺ channel blockers, including glibenclamide, barium chloride (BaCl₂), or 4-aminopyridine (4-AP). Additionally, pre-incubation with prazosin, an α-adrenoceptor blocker, significantly reduced the vasorelaxation induced by HC, whereas propranolol, a β-adrenoceptor blocker, had no effect. In addition, HC inhibited CaCl₂-induced contractions induced by both PE and caffeine in a Ca²⁺-free solution. Therefore, HC exhibited the vasorelaxant effects through an endothelium-independent mechanism. The vasodilatory effects of HC were associated with the activation of K_Ca channels, suppression of PE-induced contraction via α₁-adrenergic receptor pathways, and inhibition of CaCl₂-induced contractions by modulating intracellular Ca²⁺ release and extracellular Ca²⁺ influx in vascular cells.