Canavalia brasiliensis lectin attenuates diabetes endothelial dysfunction in rats: structural basis and implication of muscarinic/insulin receptors.

In diabetes, the endothelium acquires tendency toward vasoconstriction, inflammation, and thrombosis, and are associated with the reduced bioavailability of nitric oxide (NO). Plant lectins from the Canavalia genus elicit endothelium-dependent vasorelaxation in isolated rat aorta involving the participation of NO and the lectin domain. This study aimed to investigate ex vivo and in vivo the relaxant effect of Canavalia brasiliensis lectin (ConBr) in aorta from type 1 diabetic rats. ConBr was added at phenylephrine-contractions or acetylcholine-relaxation in isolated artery. In vivo, ConBr was injected i.v. into diabetics rats for 2 months, and aorta analyzed for histopathology, eNOS immunohistochemistry, and functional vascular response. ConBr relaxed (58 %) phenylephrine-contracted aorta of normoglycemic and diabetics. In normoglycemic, ConBr relaxant effect was inhibited by l-NAME, ODQ, 0Ca2+ and atropine, but not by TEA or by the inhibitor of PI3K/Akt (LY294002). In diabetics, ConBr effect was inhibited by l-NAME, ODQ, 0Ca2+, TEA and LY294002. In vivo, i.v. treatment with ConBr improved aorta contractility of diabetics (429.5 ± 74.7 vs. non-treated: 297.7 ± 31 mg), but unaltered acethylcholine-relaxation (52.7 ± 8.4 vs. non-treated: 55.8 ± 5.2 %). ConBr reduced aorta morphological alterations and increased eNOS expression (79 ± 3.3 vs. non-treated: 52.17 ± 2.7 %). Molecular docking of ConBr-N-glycans revealed interaction of ConBr at glycosylation points in insulin receptor. ConBr attenuates functional and morphological vascular alterations induced by diabetes, involving eNOS pathway via muscarinic and insulin receptors.