Impaired capsaicin-induced relaxation in diabetic mesenteric arteries

To investigate capsaicin-induced vasodilation in the diabetic mesenteric arteries.

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.

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.

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.