The vascular effects of rotigaptide in vivo in man

En dothelium-derived hyperpolarising factor (EDHF) causes vasorelaxation and may contribute to the release of the endogenous fibrinolytic factor, tissue-plasminogen activator (t-PA). Rotigaptide enhances communication via the connexin 43 gap junction subunit and may potentiate the vascular actions of EDHF. The aims of the present study were therefore to determine whether rotigaptide influences basal and stimulated endothelium-dependent vasodilatation and t-PA release in vivo in man. Using venous occlusion plethysmography, forearm blood flow was measured in 27 healthy volunteers during intra-brachial infusions of rotigaptide (0.25-25 nmol/min) alone, or co-administered with endothelium-dependent (acetylcholine [5-20 mu g/min] and bradykinin [30-300 pmol/min]) and independent (sodium nitroprusside 12-8 mu g/min])) vasodilators in the presence or absence of aspirin and the 'nitric oxide clamp'. The 'nitric oxide clamp' inhibits endogenous nitric oxide synthesis with L-N-monomethylarginine and restores resting blood flow with the exogenous nitric oxide donor, sodium nitroprusside. Basal blood flow was unaffected by rotigaptide (P = NS). Acetylcholine, bradykinin and sodium nitroprusside all caused dose-dependent vasodilatation in the presence and absence of aspirin and the 'nitric oxide clamp' (P <= 0.005 for all). These responses were unaffected by rotigaptide (P = NS). Bradykinin caused t-PA antigen and activity release (P = 0.04, P <= 0.0001, respectively) that was unaffected by rotigaptide. Augmentation of connexin 43 communication has no effect on basal vascular tone and does not enhance endothelium-dependent or independent vasodilatation, or t-PA release in the forearm arterial circulation of healthy men. It remains to be established whether augmentation of connexin 43 communication improves endothelial function in patients with vascular diseas

Author Correction: Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement (Nature Communications, (2018), 9, 1, (815), 10.1038/s41467-018-03156-5)

10.1038/s41467-019-09171-4Nature Communications101122