BPC 157 induces endothelium-dependent vasorelaxation in human internal mammary arteries via nitric oxide.

The stable gastric pentadecapeptide BPC 157 is recognized for its cytoprotective, pro-angiogenic, and nitric oxide (NO) modulating properties. While animal studies have shown its vasodilatory effects, direct functional evidence in human arterial tissue has been limited. Understanding BPC 157's impact on human vascular tone, particularly its interaction with the endothelium and NO signaling, is crucial for assessing its therapeutic potential in conditions like coronary artery disease or vascular dysfunction, where impaired NO bioavailability contributes to pathology.

Researchers investigated BPC 157's effects on vascular tone using residual human internal mammary artery (IMA) segments (n = 12) obtained from coronary artery bypass graft surgeries. Tissues were prepared as endothelium-intact and endothelium-denuded rings. After equilibration, rings were pre-contracted with phenylephrine (PheE; 3 × 10-6 M). Cumulative concentration-response curves for BPC 157 (0.01-1 mg/mL) were generated across five consecutive doses. To assess NO involvement, BPC 157 dose-response curves were repeated in rings pre-incubated with the nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 10-6 M). Maximum force of contraction, area under the curve, maximum response (Emax), and negative logarithm of the half-maximal effective concentration (pEC50) values were analyzed.

BPC 157 produced a concentration-dependent reduction in PheE-induced contraction in both endothelium-intact and endothelium-denuded IMA rings. Notably, vasorelaxation was significantly greater in endothelium-intact rings (p < 0.05), highlighting the critical role of the endothelium. Pre-incubation with the NOS inhibitor L-NAME significantly increased contractile responsiveness in intact rings and markedly attenuated the BPC 157-induced relaxation, confirming NO's primary role. Under NOS inhibition, the differences in relaxation between endothelium-intact and endothelium-denuded groups progressively diminished, and their concentration-response curves converged at higher concentrations. This suggests that while NO is the predominant mediator, residual vasodilatory effects indicate the involvement of additional, endothelium-independent mechanisms at higher BPC 157 concentrations. The study concluded that BPC 157 induces vasorelaxation predominantly via an endothelium-dependent NO pathway.