ABC | Volume 113, Nº2, August 2019

Original Article Casonatto et al. Citrulline and post-exercise hypotension Arq Bras Cardiol. 2019; 113(2):218-228 and hypertensive individuals. Previous studies have shown that hypertensive individuals present cardiac output reduction, 2,14 while normotensive individuals present a reduction in total peripheral resistance. 14-16 For this reason, a non-pharmacological vasodilatation strategy can help hypertensive patients to activate another PEH mechanism together with a cardiac output decrease resulting in additional PEH effects. Other experiments have observed that the plasma and salivary NO were associated with PEH after resistance 17 and aerobic exercises 17-20 in subjects with chronic diseases. Additionally, citrulline supplementation has shown promise with pre-clinical (animal) evidence for atherogenic- endothelial protection and preliminary evidence is also available for citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. 21 For these reasons, this study aimed to analyze the inter‑individual PEH responsiveness following an acute citrulline supplementation in hypertensives. Our hypotheses were: i) there would be an inter-individual variability in BP responsiveness following a single bout of aerobic exercise and ii) citrulline oral supplementation could contribute to reducing the rate of non-responders. Methods Participants After sample size calculation (see statistical analysis session), 40 hypertensive, sedentary individuals participated in the study. All volunteers (both sexes) were adults without osteoarticular disabilities and had medical authorization to practice physical exercise. Participants were recruited from an exercise program project linked to the university that offered stretching and functional exercise sessions to the external community. The study followed the Declaration of Helsinki and the Institutional Ethics Committee approved all experimental procedures and protocols (78697617.4.0000.0108). Each participant was fully informed of all potential risks and experimental procedures, after which, informed written consent was obtained. Table 1 shows the basic characteristics of the participants. Study design A double-blind, placebo-controlled, parallel-groups clinical trial was performed (Figure 1). The participants were randomly allocated (using a random number table - https://www. random.org/ ) into four different experimental groups (exercise/ citrulline [EC]; exercise/placebo [EP]; control/citrulline [CC]; control/placebo [CP]). The participants ingested a sachet, which contained citrulline malate (CM) (6 grams) or placebo (6 grams of corn starch) dissolved in water. The substances were ingested 120 minutes before the experimental or control session. Anthropometric measures were taken before the rest period. The exercise session consisted of a 5 min warm up (50% of 65% HR [heart rate] reserve) and 40 minutes of running/walking at 60-70% HR reserve on a treadmill. This was followed by a progressive cooldown (5 minutes). The exercise intensity was also evaluated based on the Borg 22 Rating of Perceived Exertion (RPE 6-20 score). The RPE was collected every 5 minutes over the course of 40 minutes during the running/walking exercise period. The exercise intensity was reduced if the participant reported RPE ≥ 15, independently of HR. In the control session, the participants remained seated in a quiet room for 40 min. After the exercise/control sessions, the BP was measured every 10 minutes over the course of 60 minutes (laboratory phase). Next, the participants were allowed 15 minutes to take a shower and change their clothes before the ambulatory BP device was attached on their arm. The ambulatory BP was recorded over 24 hours. The participants were asked to return to the laboratory the next day to remove the device. Table 1 – Characteristics of participants and antihypertensive medications Control-Placebo Control-Citrulline Exercise-Placebo Exercise-Citrulline F p Mean SD Mean SD Mean SD Mean SD Age (years) 62.3 18.7 60.6 16.8 52 15.2 58.6 8.6 0.864 0.469 Weight (kg) 77.2 16.5 76.5 9.0 79.6 17.2 72.5 13.1 0.419 0.740 Height (m) 1.66 0.11 1.59 0,08 1.61 0.08 1.58 0.09 1.309 0.286 BMI 27.9 4.2 30.6 4.6 30.8 6.5 29.1 5.8 0.625 0.603 WC (cm) 98.2 9.9 101.4 9.1 98.5 14.9 99.1 11.1 0.159 0.923 N % N % N % N % BB 3 30 5 50 5 50 3 30 ACEI 5 50 3 30 4 40 6 60 DIUR 0 0 1 10 0 0 1 10 BB+ACEI 2 20 1 10 0 0 0 0 ACEI+DIUR 0 0 0 0 0 0 0 0 BB+ACEI+DIUR 0 0 0 0 1 10 0 0 SD: standard deviation; BMI: body mass index; WC: waist circumference; BB: beta-blockers; ACEI: angiotensin-converting-enzyme inhibitor; DIUR: diuretics. 219