Investigation of functional effects and potential effect mechanisms of irisin in conducting arteries with isolated organ bath model

In this study, it was aimed to investigate the effects of irisin concentrations on vascular smooth muscle contractility in rat thoracic aortic rings, which is a conduction type artery, and the hypothesis that PKC, MEK1/2, KV, SKCa and BKCa may have roles in these effects. 84 male Wistar Albino rats of 10-12 weeks of age were used in the study. Isometric contraction responses of thoracic aortic rings isolated from experimental animals were measured with an isolated organ bath model. 7 experimental groups were formed according to the active and blocker/inhibitor substances used in the study. Preliminary contraction was created with 10-5 M PHE and concentrations in the range of 10-9-10-6 M of irisin were used in all experimental groups. The data belonging to the groups were evaluated statistically and the significance level was accepted as p<0,05. Irisin showed a statistically significant relaxant effect at concentrations of 10-8, 10-7 and 10-6 M compared to the control group (p<0,001). PKC inhibitor BIM I (p<0,001 for 10-7 M), MEK1/2 inhibitor U0126 (p<0,05 for 10-7 M), KV blocker XE-991 (p<0,001 for 10-7 M), SKCa blocker apamin (p<0,05 for 10-7 M) and BKCa blocker TEA (p<0,001 for 10-7 M) incubations inhibited relaxation responses induced by varying concentrations of irisin. However, DMSO, which is the solvent of BIM I, U0126 and XE-991, did not affect the relaxation responses to irisin (p>0,05). In conclusion, the first physiological findings regarding the functional relaxant effect of irisin on rat thoracic aorta have been obtained. In addition, this study is the first to report that irisin-induced relaxation responses may be associated with the activity of PKC, MEK1/2, voltage sensitive and calcium-activated K+ channels. Our experimental findings suggest that irisin may be a useful agent in the prevention and treatment of cardiovascular diseases associated with abnormal vasoconstriction such as hypertension and atherosclerosis.