Short-term administration of L-citrulline augments cardiac vagal control and reduces blood pressure in response to high-intensity exercise in untreated hypertensive males.

High-intensity exercise (HIE) improves cardiorespiratory fitness but also acutely increases autonomic and hemodynamic stress in hypertensive individuals. L-citrulline augments nitric-oxide bioavailability and buffers these responses. We conducted a robust crossover trial in untreated hypertensive males (n = 12) to test whether short-term L-citrulline supplementation (6 g·day⁻¹ for 6 days) modifies cardio-autonomic and hemodynamic responses after HIE. Heart-rate variability (HRV), systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP]), heart rate (HR), pulse pressure (PP), and rate-pressure product (RPP) were assessed. Mixed-effects modelling indicated that L-citrulline improved cardio-autonomic regulation: high-frequency power (HF, an index of vagal modulation) was higher at rest and at 90-min recovery; time-domain index standard deviation of normal-to-normal intervals (SDNN, representing overall autonomic activity) was increased at rest; and low-frequency power (LF) and LF/HF ratios were lower across time (condition and condition × time effects, all p ≤ 0.005). L-citrulline reduced SBP at rest (- 18.7 mmHg, p ≤ 0.005) and immediately after exercise (- 26.3 mmHg, p ≤ 0.005); DBP and MAP were lower across the recovery period (all p < 0.001). HR was reduced from 15 to 90 min post-exercise values (p ≤ 0.005), and RPP was lower immediately post-exercise (p ≤ 0.005), indicating reduced myocardial oxygen demand during this period. PP was lower immediately post-exercise (p ≤ 0.005). Supplementation with L-citrulline for six days enhanced cardiovascular recovery after HIE by blunting surges in cardiac, and BP workload, and may assist in improving the clinical efficacy of HIE in hypertensive subjects.