Levodopa and exercise: hemodynamic consequences in people with Parkinson's disease

Erin Suttman; Fabio Laginestra; Danilo Iannetta; Jeremy Alpenglow; Kanokwan Bunsawat; Ryan Broxterman; Guillaume Lamotte; Markus Amann

doi:10.1152/physiol.2026.41.S1.2341053

Abstract only Background: Dopaminergic medications, such as levodopa (LD), are the primary therapy for managing motor impairments in people with Parkinson’s disease (PD). Current evidence suggests that LD may adversely affect vascular function by impairing the endothelium and/or autonomic cardiovascular control mechanisms. While these effects likely contribute to the decrease in arterial blood pressure (MAP) at rest, the influence of LD on cardiovascular regulation during exercise remains unclear. Reductions in MAP during exercise may compromise cerebral perfusion and peripheral hemodynamics, potentially exacerbating cognitive and motor deficits, and neuromuscular fatigue. Therefore, we assessed central and peripheral hemodynamic responses during exercise, hypothesizing LD would lower MAP and impair peripheral hemodynamics. Methods: On separate days and in random order, 9 patients with idiopathic PD (69 ± 9 y) performed incremental single-leg knee-extension exercise (3 W + 3-5 W/2-min) to task failure while optimally treated with LD (LD-ON) or after LD was withdrawn for at least 12-hours (LD-OFF). MAP and cardiac output (CO) were continuously monitored with finger plethysmography, and leg blood flow (LBF) was quantified using Doppler ultrasound via femoral artery. Data were averaged over the last minute of each work rate. Leg vascular conductance (LVC) and systemic vascular conductance (SVC) were calculated as LBF/MAP and CO/MAP, respectively. Paired t-tests were used to identify ON vs OFF differences at rest. Linear mixed-effects models were applied to determine main and interaction effects of LD on hemodynamic variables, with random effects included for repeated measures. Results: Including MAP (p = 0.07), hemodynamic variables during upright, seated rest were not significantly different between LD-ON vs LD-OFF. Peak power output was not different between the two conditions (p = 0.93). Consistently throughout exercise, MAP was ~7-10% lower (p < 0.01), while LBF, CO, LVC, and SVC were higher during LD-ON vs LD-OFF (all p < 0.01). Interaction effects between medication status and work rate were observed for LBF (p = 0.01) and LVC (p = 0.05), which exhibited increased positive gains during LD-ON. Conclusions: Despite little effect during upright sitting, LD substantially altered the hemodynamic response to exercise. The steady LD-induced reduction in MAP was accompanied by consistently augmented local and systemic vasodilation, and an exaggerated CO response. The markedly elevated LVC and SVC during LD-ON imply a disruption of the normal vascular constraint that typically preserves MAP during exercise. However, the full impact of LD on MAP was presumably masked by the likely baroreflex-mediated rise in CO. Moreover, the progressively widening differences in LBF and LVC (but not SVC) between LD-ON and LD-OFF with increasing work rate suggest that the vascular impact of LD becomes more pronounced at higher exercise intensities, particularly within the exercising limb musculature. Potential mechanisms include: 1) reduced sympathetic vasomotor outflow or vascular transduction, 2) excessive endothelial-mediated vasodilation, or 3) increased functional sympatholysis. In conclusion, LD impairs vascular mechanisms that normally stabilize MAP during physical activities. This may increase the risk for syncope and other adverse events and should therefore be considered during exercise prescription and pharmacological management. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Levodopa and exercise: hemodynamic consequences in people with Parkinson's disease

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