Endothelium-Dependent Nitric Oxide-Mediated Vasorelaxant Effects of BPC 157 in Human Internal Mammary Artery

Background/Objectives: Body Protection Compound-157 (BPC 157) is a stable gastric pentadecapeptide with cytoprotective, pro-angiogenic, and nitric oxide (NO)-modulating properties that has gained increasing attention for its therapeutic potential. Although vasodilatory effects have been demonstrated in animal models, functional evidence in human arterial tissue remains limited. This study investigated the effects of BPC 157 on vascular tone in human internal mammary artery (IMA) rings and evaluated the contribution of endothelial NO signaling. Methods: Residual IMA segments obtained from elective coronary artery bypass graft surgeries (n = 12) were dissected into endothelium-intact and endothelium-denuded rings. Following equilibration, the rings were challenged by phenylephrine (PheE; 3 × 10^-6 M) to induce contraction. Cumulative concentration-response curves of BPC 157 (0.01-1 mg/mL) for five consecutive doses were constructed. The involvement of NO was assessed by BPC 157 dose-response curves in the nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 10^-6 M) pre-incubated rings. Maximum force of contraction, area under the curve, maximum response (Emax), and negative logarithm of the half-maximal effective concentration (pEC50) values were analyzed. Results: BPC 157 produced a concentration-dependent reduction in PheE-induced contraction in both groups, with significantly greater relaxation in endothelium-intact rings (p < 0.05). L-NAME increased contractile responsiveness in intact rings and attenuated BPC 157-induced relaxation. Under NOS inhibition, differences between groups progressively diminished and concentration-response curves converged at higher concentrations. Emax analysis demonstrated that endothelial integrity markedly enhanced maximal vasorelaxation, whereas this advantage was largely abolished after NOS inhibition. Conclusions: BPC 157 induces concentration-dependent vasorelaxation in human arterial tissue, predominantly mediated via an endothelium-dependent NO pathway. Endothelial integrity primarily enhances maximal efficacy, while residual effects indicate additional mechanisms. These findings provide early mechanistic evidence for the vascular activity of BPC 157, although further molecular and in vivo studies are required to clarify its clinical relevance.