Vasorelaxing Effect of Hydrolyzed Collagen from Salmon Skin in the Thoracic Aorta and Underlying Mechanisms

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 KCa 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.