Normal perivascular sensory dilator nerve function in arteries of Zucker diabetic fatty rats

Background Type II diabetes in humans is associated with pathology of both the cardiovascular and peripheral sensory nervous systems. Because abnormal vasodilator responses have been reported in animals of type II diabetes and perivascular sensory nerves are a source of vasodilator substances, we tested the hypothesis that sensory nerve-dependent relaxation is abnormal in arteries of the Zucker diabetic fatty (ZDF) rat model of type II diabetes. Methods The ZDF rats and genetic controls were studied at 26 weeks of age. Tail-cuff systolic blood pressure (BP) was measured, serum was obtained for chemical determinations, and mesenteric branch arteries were isolated for wire myograph analysis and confocal-based measurement of calcitonin gene-related peptide (CGRP) positive nerve density. Results No differences in BP were detected. Serum glucose, triglycerides, and cholesterol were significantly elevated in ZDF. Sensory nerve-dependent vasodilation was assessed by measuring relaxation of phenylephrine preconstricted arterial segments to cumulative addition of divalent calcium ion (Ca2+) or capsaicin. Neither Ca2+- nor capsaicin-induced relaxation were different in ZDF versus control (maximal ZDF response to Ca2+ = 64% ± 2% v 59% ± 4%; ED50 for Ca2+ = 3.7 ± 0.5 mmol/L v 3.2 ± 0.5 mmol/L; N = 5, P = not significant [NS]; maximal ZDF response to CAPSAICIN = 68% ± 9% v 74% ± 4%; ZDF ED50 = 3.8 ± 0.5 nmol/L v 9.8 ± 7 nmol/L; N = 5, P = NS). In contrast, the maximal relaxation response to acetylcholine was impaired in ZDF (maximal ZDF RESPONSE = 83% ± 5% v 94% ± 2%, N = 4, P = .039; ED50 for ACETYLCHOLINE = 8.1 ± 2.9 nmol/L for ZDF v 33.5 ± 18.2; N = 4 per group, P = .086). The CGRP positive nerve density was not different between groups. Conclusions Blood pressure, perivascular sensory nerve CGRP content, and dilator function is normal in the ZDF model of type II diabetes, whereas endothelium-dependent relaxation is impaired.