Impaired Capsaicin-induced Relaxation Of Mesenteric Arteries In Diabetic Rats

Background:Diabetes mellitus is a chronic metabolic disease caused by either lack of insulin secretion or hyposensitivity to insulin, including metabolic disorder of carbohydrate, fat and protein, and is chiefly characterized by hyperglycemia. Diabetes mellitus usually associates with cardiovascular complications which are the principal cause of diabetic mortality. Therefore it is of clinical importance to find available drugs for their prevention and treatment. Lots of research have showed capsaicin exert many kinds of bioactivity, such as antioxidants, promotion of energy metabolism and suppression of fat accumulation, and anti-inflammatories, and analgesic effect. However, little is known about whether capsaicin (CAP) has the same effects on diabetic resistant arteries as large vessels. Objective:To investigate the vasodilation effect of CAP and its underlying mechanisms on rat mesenteric artery. Methods:The third branch of the superior mesenteric artery in male Sprague-Dawley rat or diabetic rat model induced by streptozotocin (60mg/kg, i.p.) was quickly excised. Periadventitial fats and connective tissues were removed and the mesenteric artery was dissected into2mm rings. Each ring was placed in a5ml organ bath of DMT610M system and the tension was recorded. Moreover, biochemical indicator, such as calcitonin gene-related peptide (CGRP) and substance P (SP) activity were detected in the PSS. TRPV1protein expression of diabetic rat mesenteric artery was measured by western blot. Results:① CAP (10-9～10-5mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine, and the vasodilation of endothelium-intact mesenteric artery was better than in endothelium-denuded artery. Pretreatment with either L-NAME, an inhibitor of nitric oxide synthase (NOS), or CGRP8-37, an antagonist of CGRP, for30min significantly attenuated the relaxation induced by CAP. The vasodilation of CAP could be completely blocked by L-NAME+CGRP8-37.②Compared with normal control group, CAP-induced relaxation in diabetic resistant artery was impared significantly, while SNP-induced vasorelaxation was not changed. Pretreatment with L-NAME or CGRP8-37, CAP-induced vasorelaxation of diabetic rat was much more blocked than normal control group. Exogenous CGRP-induced vasorelaxation of diabetic rat was less than normal control group. In diabetic rat serum and diabetic group PSS, the level of CGRP was much lower than normal control group. What’s more, TRPV1protein expression in diabetic rat mesenteric artery was lower than normal control group. Conclusions:CAP had partial endothelium-dependent relaxation in rat mesenteric artery, which may be mediated by activating the endothelial NOS-NO pathway. The endothelium-independent relaxation in rat mesenteric artery induced by CAP may be mediated by CGRP. Impaired CAP-induced relaxation in diabetic mesenteric artery maybe associated with following mechanisms:①The level of NOS-NO was decresed significantly in the diabetic endothelial dysfuntion.②Impaired CGRP-induced vasodialation of mesenteric artery in diabetic rat.③TRPV1protein expression was decreased in diabetic mesenteric artery which might reduce CGRP release. This is also an important mechanism contributing to the impared CAP-induced vasodiation.