Copper-promoted hypercontraction of rat aortic rings and its mitigation by natural molecules

Abstract

Abstract Previous studies on copper (Cu) toxicity suggest a causal relationship between Cu overdose and abnormal vascular tone, hypertension, and cardiovascular abnormalities. However, the direct effect of free Cu in aortic smooth muscle contraction has been largely unexamined. In this study direct effect of Cu (II) on isolated rat aortic rings in the organ bath system is investigated. The contribution of different contractile factors in Cu (II)-mediated hypercontraction was examined by employing inhibitors of respective factors in aortic rings. Results obtained suggest that the exposure to 6µM Cu (II) causes a significant increase of 42% to phenylephrine (PE)- stimulated contractile magnitude in endothelium-intact aortic rings. Major contributors of Cu (II)-mediated hypercontraction in aortic rings are observed to be ROS generation and calcium influx via voltage-gated calcium channels. Cu (II)-mediated hypercontraction does not appear to involve COX-mediated pathways. Reported natural smooth muscle relaxants, linalool, carvone, eugenol, and thymol are investigated as mitigators of Cu (II)-mediated hypercontraction. Linalool and carvone are found to mitigate elevated aortic contraction in presence of Cu (II) whereas eugenol and thymol were unable to effectively mitigate the contractile effect of Cu (II).