Molecular mechanisms of the cardiovascular protective effects of imidazoline-1 receptor in diabetes

Diabetes can lead to cardiovascular damage overtime via several mechanisms. One of these mechanisms is sympathetic overactivity. As in diabetes, glucose, insulin and nonesterified fatty acids are strong stimulants to sympathetic nervous system. This sympathetic overactivation can lead to cardiovascular function deterioration. Therefore, sympathoinhibition will be a good approach to protect against cardiovascular complications. This can be achieved through either a2 or I-1 receptor activation. I-1 receptors are mainly involved in: (i) Cardiovascular regulation. (ii) Ameliorating metabolic abnormalities. Rilmendine and moxonidine are well known selective I-1 agonists. Agmantine, an arginine metabolite, and imidazole-4-acetic acid ribotide (IAA-RP) are endogenous ligands to imidazoline receptors. LNP 509, LNP 911 and S 23515 are newly developed I-1 agonists and they are highly selective. Their hypotensive actions are well documented but the molecular mechanisms of their cardiovascular protective actions are not known. The proposed studies will focus on the role of neuronal signaling triggered by central I-1 receptor activation in these protective cardiovascular effects.

Scholars @ ECU