Anti-smoking drugs cytisine and varenicline reduce cardiac reperfusion injury in rat model of myocardial ischemia

Evidence to date indicates that activation of nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury from ischemia and subsequent reperfusion. The use of nAChR agonists in various animal models leads to a reduction in reperfusion injury. Earlier this effect was shown for the agonists of a7 nAChR subtype. In this work, we demonstrated the expression of mRNA encoding a4, a6 and 132 nAChR subunits in the left ventricle of rat heart. In a rat model of myocardial ischemia, we studied the effect of a4132 nAChR agonists cytisine and varenicline, medicines used for the treatment of nicotine addiction, and found them to significantly reduce myocardium ischemia-reperfusion injury, varenicline manifesting a higher protection. Dihydro-13-erythroidine, antagonist of a4132 nAChR, as well as methyllycaconitine, antagonist of a7 and a6132-containing nAChR, prevented protective effect of varenicline. This together with the presence of a4, a6 and 132 subunit mRNA in the left ventricule of rat heart raises the possibility that the varenicline effect is mediated by a4132 as well as by a7 and/or a6132-containing receptors. Our results point to a new way for the use of cytisine and varenicline as cardioprotective agents. (c) 2023 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Automated summary

Evidence suggests that activating nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury caused by ischemia and reperfusion. In this study, the expression of a4, a6, and a132 nAChR subunits in the rat heart's left ventricle was demonstrated. The nAChR agonists cytisine and varenicline, commonly used for nicotine addiction treatment, were found to significantly reduce myocardial ischemia-reperfusion injury, with varenicline showing greater protection. The presence of a4132, a7, and/or a6132-containing receptors suggests that the protective effect of varenicline may be mediated by these subunits. These findings indicate a potential new use for cytisine and varenicline as cardioprotective agents.