The impact of age and exercise training on endothelial-mediated mechanisms of vasodilation during passive leg movement in males

Passive leg movement (PLM) offers a robust method for assessing vascular function; however, the interactions among age, endothelial-mediated vasodilatory mechanisms, and exercise training-induced PLM modulation remain poorly understood. To address these gaps, the vasodilatory responses to PLM, quantified as leg vascular conductance (LVC) dynamics, were measured in younger (n = 9, 25 ± 4 yr) and older males (n = 9, 69 ± 5 yr) before and after 8 wk of single-leg knee-extension exercise training. Femoral arterial drug infusions pharmacologically dissected the contribution of the prostaglandin (PG) and epoxyeicosatrienoic acids (EETs) pathways to the residual, nitric oxide (NO)-independent component of the PLM vasodilatory response. Interrogation of these vasodilatory pathways was assessed by PLM under three conditions: control (CON), inhibition of nitric oxide synthase (NOS) alone (NG-monomethyl-l-arginine, l-NMMA), and combined inhibition of NOS, cyclooxygenase (ketorolac tromethamine, KET), and cytochrome P450 (fluconazole, FLUC) (l-NMMA + KET + FLUC). Exercise training improved the PLM vasodilatory (LVC area under the curve) response in younger (4.3 ± 1.4 to 7.1 ± 4.3 mL·mmHg⁻¹, P < 0.05) but not older (2.2 ± 1.4 to 2.4 ± 1.2 mL·mmHg⁻¹, P = 0.97) males. In younger males, both l-NMMA and l-NMMA + KET + FLUC elicited significant (both P < 0.05) and similar (P = 0.99) reductions in the PLM vasodilatory response, with no effect of exercise training (P = 0.90). Neither l-NMMA nor l-NMMA + KET + FLUC attenuated the PLM vasodilatory response in older males before or after exercise training (P = 0.68 and P = 0.51, respectively). Together, these results indicate 8 wk of single-leg knee-extension exercise training improves the vasodilatory response to PLM in younger, but not older males, and does not alter the contribution of NO or the combined contribution of PG and EETs to PLM-induced vasodilation.NEW & NOTEWORTHY This study examined the impact of age and exercise training on vasodilatory mechanisms associated with passive leg movement (PLM), including nitric oxide (NO), prostaglandins (PGs), and endothelial-derived hyperpolarizing factors (EDHFs) in younger and older adult males. Following 8 wk of single-leg knee-extension exercise training, PLM was improved in younger but not older males; however, the improvement was not associated with altered contribution from NO, PG, or EDHF, suggesting other vasodilatory mechanisms may be involved.