title: Impaired capsaicin-induced relaxation in diabetic mesenteric arteries.
abstract: OBJECTIVE
  To investigate capsaicin-induced vasodilation in the diabetic mesenteric arteries.
  
  
  METHODS
  A diabetic rat model was established by intraperitoneal injection of streptozotocin after a 12-h fast. At 12 weeks post-injection, the third branch of the mesenteric artery was dissected out and prepared for vascular reactivity assessment. Capsaicin, capsazepine, N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME), sodium nitroprusside (SNP), calcitonin gene-related peptide 8-37 (CGRP8-37), calcitonin gene-related peptide (CGRP), and substance P (SP) were added to investigate subsequent alterations in vascular activity. Plasma and physiological salt solution (PSS) levels of CGRP and SP were measured using radioimmunoassay. The expression of transient receptor potential vanilloid 1 (TRPV1) and phospho-eNOS were determined using Western blot analysis, and nitric oxide (NO) production was measured using a fluorescence probe.
  
  
  RESULTS
  The dilation effect of capsaicin was weaker under the diabetic than control conditions. Capsazepine, L-NAME, and CGRP8-37 attenuated capsaicin-induced vasorelaxation significantly in the diabetic vascular rings. Exogenous CGRP elicited dose-dependent vasodilation in the control arteries, whereas the dilation effect was reduced under diabetic conditions. Plasma and PSS CGRP levels were attenuated and mesenteric artery TRPV1 expression was decreased in the diabetic rats. Phospho-eNOS levels were augmented, and NO production increased following the administration of capsaicin.
  
  
  CONCLUSIONS
  Decreased expression of TRPV1 and associated neuropeptide release contributed to the impaired capsaicin-induced vasodilation in diabetic mesenteric arteries. Furthermore, an endothelium-dependent NO-related pathway was involved in capsaicin-induced vasodilation.
authors.affiliation: Department of Cardiovascular Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Sciences, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu 322000, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Zewei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Cardiovascular Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Cardiovascular Sciences, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Sciences, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. Electronic address: zlrylnn@126.com.
authors.forename: Liangrong
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester
keywords: CGRP; Capsaicin; Diabetes mellitus; Mesenteric artery; Nitric oxide; TRPV1