Moderate Intensity Exercise Causes a Shift in the Relative Importance of the Endothelium-Dependent Relaxing Factors in Mesenteric Arteries of Male UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) Rats
Over the past decade obesity and type 2 diabetes (T2D) have reached epidemic levels worldwide. Cardiovascular disease (CVD) is one of the leading causes of mortality and morbidity in diabetic patients. Regular aerobic exercise is a well-characterized lifestyle intervention that improves endothelial dysfunction, insulin resistance, and CVD risk in T2D. However, there are still debates regarding the duration and intensity of exercise required to ameliorate the deleterious metabolic perturbations in patients with T2D. The objective of this study was to investigate the effects of moderate intensity exercise (MIE) on vascular reactivity of mesenteric artery (MA) of male UC Davis Type-2 Diabetes Mellitus Rat (UCD-T2DM) model. Specifically, we examined whether there were changes in the relative contributions of endothelium-derived relaxing factors in modulating vascular reactivity of MA from exercise-trained compared with control sedentary UCD-T2DM rats. Age-matched male control and UCD-T2DM rats underwent forced treadmill exercise (E) or remained sedentary (S) for 8 weeks. Endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh, 10-8 to 10-5 M) were measured in precontracted MA before and after indomethacin (10µM), a cyclooxygenase (COX) inhibitor; followed by addition of L-NAME (200µM), a nitric oxide synthase (NOS) inhibitor; followed by combination of apamin (1 µM) and TRAM-34 (1 µM) (SKCa and IKCa blockers, respectively). The diabetic exercise trained (DE) rats exhibited decreased visceral adiposity and plasma triglyceride levels compared with the diabetic sedentary (DS) group. However, MIE did not alter plasma glucose or insulin concentrations in either nondiabetic or diabetic UCD-T2DM Rats. Both sensitivity and maximal responses (Emax) to ACh were significantly reduced in MA from DS rats compared with those in control sedentary (CS). MIE improved the Emax to ACh only in MA of DE group. Inhibition of COX enhanced Emax to ACh in DS arteries suggesting the elevation of contractile COX metabolites in the DS group. The addition of L-NAME resulted in a reduction in ACh relaxation of arteries from both CS and DS rats, however the effect was more prominent in DS group, suggesting the contribution of NO was enhanced (or endothelium-dependent hyperpolarizing factor (EDHF)-type relaxation was diminished) in DS arteries. Remarkably, MIE reversed the loss of EDHF-type relaxation in UCD-T2DM Rats. Unlike in the DS group, inhibition of COX had no effect on ACh response in MA of the DE group, suggesting that MIE may cause a shift from contractile COX to NO and EDHF-type relaxation in UCD-T2DM Rats. In conclusion, we provide the first evidence for a positive impact of moderate exercise on mesenteric arterial function in male UCD-T2DM Rats, likely mediated by a contribution of EDHF-type (NO and prostanoid-independent) responses.
Livesey, J. C.,
Graham, J. L.,
Stanhope, K. L.,
Havel, P. J.,
Moderate Intensity Exercise Causes a Shift in the Relative Importance of the Endothelium-Dependent Relaxing Factors in Mesenteric Arteries of Male UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) Rats.
FASEB Journal, 35(Supp 1),