Tao Sun1, Zheng Guo2, Chao-Jie Liu1, Mu-Rong Li1, Tu-Ping Li1, Xin Wang1, Da-Jiang Yuan1. 1. Department of Anesthesiology, Shanxi Medical University, 56 Xinjian Nan Road, Taiyuan 030001, Shanxi, China. 2. Department of Anesthesiology, Shanxi Medical University, 56 Xinjian Nan Road, Taiyuan 030001, Shanxi, China; Department of Anesthesiology, Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan 030001, Shanxi, China; Key Laboratory of Cellular Physiology at Shanxi Medical University, National Education Commission, 56 Xinjian Nan Road, Taiyuan 030001, Shanxi, China. Electronic address: guozheng713@163.com.
Abstract
BACKGROUND: Calcitonin gene-related peptide (CGRP) plays an important role in cardiovascular regulation, which was found reduced in serum of diabetic patients. To test the hypothesis that lack of CGRP in myocardium is associated with diabetic cardiac dysfunction, which may be improved by preservation of CGRP in diabetic rats. METHODS AND RESULTS: Diabetes was induced in male Sprague-Dawley rats by streptozotocin (50mg/kg). Two groups of the diabetic rats, one fed with standard laboratory chew and another with the laboratory food plus hot pepper (containing 0.0174% of capsaicin), to stimulate production and release of CGRP. Cardiac functions were evaluated by measurements of intraventricular pressures after 8weeks of development of diabetes. Transient receptor potential vanilloid type 1 (TRPV1), CGRP, β1-adreneregic receptor and norepinephrine were analyzed. Significantly lower levels of TRPV1 and CGRP were detected in the thoracic dorsal root ganglia (DRG) and myocardium of the diabetic animals, along with significant decline in left ventricular systolic pressure (by 24%) and heart rate (by 25%) and increase of the end-diastolic pressure (by 83%) with obvious reduction of CGRP in the DRG, by 41%, the myocardium (by 30%) and the serum (by 20%). The cardiac performance, the TRPV1 and the CGRP in the diabetic animals fed with hot pepper were well preserved. No any significant change in β1-adreneregic receptor and norepinephrine was detected. CONCLUSION: The findings may suggest a novel mechanism underlying diabetic cardiac dysfunctions via impairing TRPV1-CGRP pathway in myocardium. Preservation of the TRPV1-CGRP mechanism may prevent the development of cardiac dysfunction in diabetes.
BACKGROUND:Calcitonin gene-related peptide (CGRP) plays an important role in cardiovascular regulation, which was found reduced in serum of diabeticpatients. To test the hypothesis that lack of CGRP in myocardium is associated with diabetic cardiac dysfunction, which may be improved by preservation of CGRP in diabeticrats. METHODS AND RESULTS:Diabetes was induced in male Sprague-Dawley rats by streptozotocin (50mg/kg). Two groups of the diabeticrats, one fed with standard laboratory chew and another with the laboratory food plus hot pepper (containing 0.0174% of capsaicin), to stimulate production and release of CGRP. Cardiac functions were evaluated by measurements of intraventricular pressures after 8weeks of development of diabetes. Transient receptor potential vanilloid type 1 (TRPV1), CGRP, β1-adreneregic receptor and norepinephrine were analyzed. Significantly lower levels of TRPV1 and CGRP were detected in the thoracic dorsal root ganglia (DRG) and myocardium of the diabetic animals, along with significant decline in left ventricular systolic pressure (by 24%) and heart rate (by 25%) and increase of the end-diastolic pressure (by 83%) with obvious reduction of CGRP in the DRG, by 41%, the myocardium (by 30%) and the serum (by 20%). The cardiac performance, the TRPV1 and the CGRP in the diabetic animals fed with hot pepper were well preserved. No any significant change in β1-adreneregic receptor and norepinephrine was detected. CONCLUSION: The findings may suggest a novel mechanism underlying diabetic cardiac dysfunctions via impairing TRPV1-CGRP pathway in myocardium. Preservation of the TRPV1-CGRP mechanism may prevent the development of cardiac dysfunction in diabetes.