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Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.

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An acute bout of exercise elicits a rapid, potentially deleterious, reduction in blood glucose in patients with type 1 diabetes mellitus (T1DM). In the current study, we examined whether a 10-week aerobic training program could alleviate the rapid exercise-associated reduction in blood glucose through changes in the glucoregulatory hormonal response or increased hepatic glycogen storage in an insulin-treated rat model of T1DM. Thirty-two male Sprague-Dawley rats were divided evenly into 4 groups: non-T1DM sedentary (C) (n = 8), non-T1DM exercised (CX) (n = 8), T1DM sedentary (D) (n = 8), and T1DM exercised (DX) (n = 8). Exercise training consisted of treadmill running for 5 days/week (1 h, 27 m/min, 6% grade) for 10 weeks. T1DM was induced by multiple streptozotocin injections (20 mg/kg) followed by implantation of subcutaneous insulin pellets. At week 1, an acute exercise bout led to a significant reduction in blood glucose in DX (p < 0.05), whereas CX exhibited an increase in blood glucose (p < 0.05). During acute exercise, serum epinephrine was increased in both DX and CX (p < 0.05), whereas serum glucagon was increased during recovery only in CX (p < 0.01). Following aerobic training in DX, the exercise-mediated reduction in blood glucose remained; however, serum glucagon increased to the same extent as in CX (p < 0.05). DX exhibited significantly less hepatic glycogen (p < 0.001) despite elevations in glycogenic proteins in the liver (p < 0.05). Elevated serum epinephrine and decreased hepatic adrenergic receptor expression were also evident in DX (p < 0.05). In summary, despite aerobic training in DX, abrupt blood glucose reductions and hepatic glycogen deficiencies were evident. These data suggest that sympathetic overactivity may contribute to deficiencies in hepatic glycogen storage.

Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9–17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM.

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Murias JM, Grise KN, Jiang M, Kowalchuk H, Melling CWJ, Noble EG. Acute endurance exercise induces changes in vasorelaxation responses that are vessel-specific. Am J Physiol Regul Integr Comp Physiol 304: R574 -R580, 2013. First published December 12, 2012 doi:10.1152/ajpregu.00508.2012.-The dynamic adjustment and amplitude of the endothelium-dependent vasorelaxation of the carotid, aorta, iliac, and femoral vessels were measured in response to acute low-(LI) or high-intensity (HI) endurance exercise. Vasorelaxation to 10 Ϫ4 M ACh was evaluated in 10 control, 10 LI, and 10 HI rats. Two-millimeter sections of carotid, aorta, iliac, and femoral arteries were mounted onto a myography system. Vasorelaxation responses were modeled as a monoexponential function. The overall (control, 10.5 Ϯ 6.0 s; LI, 10.4 Ϯ 5.7 s; HI, 11.0 Ϯ 6.9 s) and time-to-steady-state (control, 47.6 Ϯ 24.0 s; LI, 46.2 Ϯ 22.8 s; HI, 49.1 Ϯ 28.3 s) was similar in LI, HI, and control (P Ͼ 0.05). The overall (average of four vessel-type) % vasorelaxation was larger in LI (73 Ϯ 16%) and HI (73 Ϯ 16%) than in control (66 Ϯ 19%) (P Ͻ 0.05). The overall rate of vasorelaxation was greater in LI (1.9 Ϯ 0.9%·s Ϫ1) and HI (1.9 Ϯ 1.1%·s Ϫ1) compared with control (1.6 Ϯ 0.7%·s Ϫ1 ) (P Ͻ 0.05). The vessel-specific responses (average response for the three conditions) showed that carotid displayed a slower adjustment (, 18.9 Ϯ 4.4 s; time-to-steady-state, 80.4 Ϯ 18.4 s) compared with the aorta (, 10.3 Ϯ 3.8 s; time-to-steady-state, 46.3 Ϯ 15.2 s), the iliac (, 6.3 Ϯ 2.1 s; time-to-steady-state, 30.3 Ϯ 9.0 s), and the femoral (, 6.0 Ϯ 1.9 s; time-to-steady-state, 29.3 Ϯ 8.4 s). The % vasorelaxation was larger in the carotid (82 Ϯ 14%) than in the aorta (67 Ϯ 16%), iliac (61 Ϯ 13%), and femoral (71 Ϯ 19%) (P Ͼ 0.05). The rate of vasorelaxation was carotid (1.1 Ϯ 0.2%·s, and femoral (2.6 Ϯ 1.0%·s Ϫ1 ). In conclusion, an acute bout of endurance exercise increased vascular responsiveness. The dynamic and percent adjustments were vessel-specific with vessel function likely determining the response. endothelium-dependent vasorelaxation; vessel myography; vascular responsiveness; vascular kinetics THE MATCHING OF BLOOD FLOW to the metabolic demands for oxygen and other nutrients throughout different organs is of critical importance to maintain cellular energetics and homeostasis (2). In this regard, relaxation of the vascular smooth muscle through diffusion of nitric oxide (NO) produced in the endothelial cells through the activation of endothelial NO synthase (e-NOS) has been shown to be fundamental (6,9,29). Although the positive effects of endurance exercise training on vascular responsiveness (and more specifically endothelium-dependent vasodilation) have been demonstrated (12,13,15,28), the effects of an acute bout of exercise on vascular responsiveness are poorly understood. For instance, an early study by Delp and Laughlin (5) showed no changes in the vasorelaxation response to a given dose of ACh in the aorta arteries of rats 24 h after a single, 1-h bout of...

This study tested the hypothesis that acute hyperglycemia reduces sciatic nerve blood flow in Sprague-Dawley rats. Anesthetized rats underwent cannulation of their right jugular vein (for anesthetic/nutrient/drug infusion) and right carotid artery (for continuous blood pressure measurement via pressure transducer). The left sciatic nerve was exposed and nerve blood velocity (NBV) was assessed from an arterial segment lying superficially along the sciatic nerve (Doppler ultrasound, 40 MHz). NBV and mean arterial pressure (MAP) values were collected, and an index of nerve vascular conductance (NVC) was established (NBV/MAP) at baseline and at 5, 10, 20, and 30 min (and 80 min for insulin) following 1) low glucose infusion, 1 g/kg (50% solution); 2) high glucose infusion, 3 g/kg; 3) high glucose infusion in the absence of a functioning pancreas; 4) euglycemic hyperinsulinemic clamp-insulin infusion (10 mU·kg⁻¹·min⁻¹; 0.4 IU/ml); 5) high glucose infusion + NG-nitro-L-arginine methyl ester (L-NAME) infusion (30 mg/kg); and 6) L-NAME alone followed 20 min later by high glucose infusion. High glucose infusion increased NVC by ~120% relative to baseline (P < 0.001), and this dilation was attenuated in rats without a functioning pancreas (i.e., without insulin secretion) (P = 0.004) and following L-NAME infusion (P = 0.011). Therefore, the vasodilation in rat sciatic nerve during glucose infusion was dependent upon the insulin response and acted through a nitric oxide synthase pathway.