Sericin-derived oligopeptides obtained from silk cocoons were investigated for the in vivo hypotensive effect and investigated for the underlying mechanism involved in vasodilation in isolated rat thoracic aorta. In normotensive anesthetized rats, oligopeptides induced an immediate and transient hypotensive activity. In rat aortic rings, oligopeptides induced a concentration-dependent vasorelaxation in vessels precontracted with both KCl and phenylephrine (PE) with endothelium-intact or endothelium-denuded rings. In endothelium-intact rings, pretreatment with Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100？μM), an inhibitor of the NO synthase (NOS) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1？μM), a selective inhibitor of the guanylyl cyclase enzyme, significantly reduced the relaxant effect of oligopeptides. However, indomethacin, an inhibitor of the cyclooxygenase, had no effect on oligopeptides-induced relaxation. In addition, pretreatment with tetraethylammonium (TEA, 5？mM) reduced the maximal relaxant effect induced by oligopeptides. By contrast, relaxation was not affected by 4-aminopyridine (4-AP, 1？mM), glibenclamide (10？μM), or barium chloride (BaCl2, 1？mM). In depolarization Ca2+-free solution, oligopeptides inhibited calcium chloride- (CaCl2-) induced contraction in endothelium-denuded rings in a concentration-dependent manner. Nevertheless, oligopeptides attenuated transient contractions in Ca2+-free medium containing EGTA (1？mM) induced by 1？μM PE, but they were not affected by 20？mM caffeine. It is obvious that potent vasodilation effect of oligopeptides is mediated through both the endothelium and the vascular smooth muscle. 1. Introduction Peptides derived from dietary proteins have been determined to modulate physiological functions. Bioactive peptides have also elicited antihypertensive and vasodilator functions [1]. The most common underlying mechanism of bioactive peptides has been studied in angiotensin-converting enzyme (ACE) inhibition [2–4]. Although the ACE inhibitor effects of bioactive peptides are most often studied, the vasorelaxant activity has also shown an important evidence for lowering blood pressure. It is well established that dietary protein found in soy protein [5], milk casein [6], and sweet potato [7] and its hydrolysates are capable of reducing blood pressure and modulating vascular activity. Recently, there are many reports that dietary-protein-derived peptides lower blood pressure and modulate vasodilation from several sources including egg white [8], soy protein [9], and κ-casein [10].
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