Aerobic training increases skin perfusion by a nitric oxide mechanism in type 2 diabetes

Abstract

It is well known that a number of locally released vasodilatory and vasoconstrictive compounds can affect skin perfusion. This study investigated the effects of aerobic training on the contribution of nitric oxide (NO), prostaglandins (PG), and endothelial-derived hyperpolarizing factor (EDHF) in stimulated dorsal foot skin perfusion in individuals with type 2 diabetes (T2DM). Ten previously sedentary, older individuals with T2DM (57.0 ± 3.1 years) and nine sedentary controls (53.5 ± 3.2 years) were tested before and after undertaking six months of moderate aerobic training three times weekly in a supervised setting. All subjects underwent measurement of baseline (32°C) and heat-stimulated (40°C and 44°C) dorsal foot skin perfusion starting one hour after ingestion of a single, oral 325 mg dose of aspirin, a known inhibitor of PG synthesis. Before aspirin ingestion, a subcutaneous microdialysis probe was inserted into each foot dorsum to administer either saline (PG pathway only blocked by aspirin in the left foot) or L-NAME (N(G)-nitro-l-arginine methyl ester; thereby inhibiting both PG and NO pathways in the right foot). Normative data collected previously on subjects undergoing saline administration via microdialysis without aspirin ingestion served as a control group. Significantly lower responsiveness of maximal perfusion was found with the EDHF pathway alone unblocked compared with NO and EDHF unblocked after training. Maximal suppression attributable directly to NO, PG, and EDHF was not significantly different when examined by subject group and training status. However, contributions of NO, PG, and EDHF to maximal perfusion were significantly increased, decreased, and unchanged by aerobic training, respectively, with diabetic and control subjects combined due to nonsignificant differences between groups. Improvements in maximally stimulated dorsal foot skin perfusion resulting from six months of aerobic training appear to have primarily an NO basis, with lesser contributions from PG following training, regardless of diabetes status.

Keywords: aerobic training; endothelial-derived hyperpolarizing factor; microdialysis; nitric oxide; prostaglandins; skin perfusion; type 2 diabetes.

Figure 1

Suppression of maximally stimulated (44°C) dorsal skin perfusion by subject group pre- and post-training. “Non-PG” conditions include oral ingestion of aspirin and systemic suppression of PG synthesis by aspirin (left foot), while “non-PG/non-NO” conditions have inhibition of PG by aspirin and add local blockade of NO via microdialysis infusion of L-NAME, a NO synthase inhibitor (right foot). These results include oral aspirin ingestion in all subjects and have not yet been compared with normative data collected without aspirin. Subject groups are differentiated by both diabetes and training status. Notes: Black bars, control subjects pre-training; gray bars, diabetic subjects pretraining; spotted bars, control subjects post-training; striped bars, diabetic subjects post-training. *P < 0.05 versus same group in non-PG; ^†P < 0.01 versus same group in non-PG. Abbreviations: PG, prostaglandins; NO, nitric oxide; L-NAME, (N(G)-nitro-larginine methyl ester); CON, controls; DM, diabetes mellitus.

Figure 2

Suppression of maximally stimulated (44°C) dorsal skin perfusion attributable directly to each vasodilator when grouped by diabetes and training status. These data are examined as a percent of suppression attributable directly to each vasodilator individually, determined using normative data collected previously in a similar subject group without oral aspirin ingestion. Subject groups are differentiated by both diabetes (DM versus controls) and pre-and post-training status. Notes: Black bars, CON Pre, control subjects pre-training; gray bars, DM Pre, type 2 diabetic subjects pre-training; spotted bars, CON Post, control subjects post-training; striped bars, DM Post, type 2 diabetic subjects post-training. Abbreviations: PG, prostaglandins; NO, nitric oxide; EDHF, endothelial-derived hyperpolarizing factor; DM, diabetes mellitus; CON, controls; Pre, pretraining; Post, post-training.

Figure 3

Relative contribution of three vasodilatory pathways in response to maximal dorsal foot skin perfusion. Due to nonsignificant differences between groups in suppression of maximally stimulated skin perfusion both pre-and post-training, these data are presented with subject groups combined. Notes: Black bars, pretraining (n = 19, CON and DM subjects combined); striped bars, post-training (n = 19, CON and DM subjects combined). *P < 0.05 pretraining versus post-training. Abbreviations: CON, controls; DM, diabetes mellitus.