ABC | Volume 113, Nº2, August 2019

Original Article Inter-Individual Responses to Citrulline Malate Oral Supplementation on Post-Exercise Hypotension in Hypertensives: A 24-Hour Analysis Juliano Casonatt o, Daniel Massaharu Enokida , Kamila Grandolfi Universidade Norte do Paraná, Londrina, PR – Brazil Mailing Address: Juliano Casonatto • Universidade Norte do Paraná - Rua Marselha, 591. Postal Code 86041-140, Londrina, PR – Brazil E-mail: juliano2608@hotmail.com Manuscript received August 28, 2018, revised manuscript October 29, 2018, accepted November 14, 2018 DOI: 10.5935/abc.20190115 Abstract Background: Studies have persuasively demonstrated that citrulline has a key role in the arginine-nitric oxide system, increasing nitric oxide bioavailability, an important mediator of peripheral vasodilation. Objective: To analyze the inter-individual post-exercise hypotension responsiveness following acute citrulline supplementation in hypertensives. Methods: Forty hypertensives were randomly assigned to one of the four experimental groups (control-placebo, control‑citrulline, exercise-placebo, and exercise-citrulline). They ingested placebo or citrulline malate [CM] (6 grams). During the exercise session, individuals performed 40 minutes of walking/running on a treadmill at 60-70% of HR reserve. For the control session, the individuals remained seated at rest for 40 minutes. Office blood pressure (BP) was taken every 10 minutes until completing 60 minutes after the experimental session. The ambulatory BP device was programmed to take the readings every 20 minutes (awake time) and every 30 minutes (sleep time) over the course of 24 hours of monitoring. Statistical significance was defined as p < 0.05. Results: Unlike the other experimental groups, there were no “non-responders” in the exercise/citrulline (EC) for “awake” (systolic and diastolic BP) and “24 hours” (diastolic BP). The effect sizes were more consistent in the EC for systolic and diastolic ambulatorial BP response. The effects were “large” (> 0.8) for “awake”, “asleep”, and “24 hours” only in the EC for diastolic BP. Conclusion: CM supplementation can increase the post-exercise hypotensive effects in hypertensives. In addition, the prevalence of non‑responders is lower when associated with aerobic exercise and CM supplementation. (Arq Bras Cardiol. 2019; 113(2):218-228) Keywords: Exercise; Hypertension; Blood Pressure Monitoring Ambulatory; Citruline; Amino Acids; Nitric Oxide; Dietary Supplements. Introduction Post-exercise hypotension (PEH) is defined as a sustained reduction in blood pressure (BP) after a single bout of exercise. 1 This transient reduction can last up to 22h after completion of an exercise session. 2 For this reason, PEH is now considered to be an important physiological phenomenon, 1 which can play a major role in BP management. It is important to emphasize that PEH is a physiological phenomenon characterized by a reduction in BP following exercise compared with pre-exercise or control session values, with may be sustained for some hours. 3 Therefore, for the PEH to be clinically significant, an important magnitude and maintenance of this reduction for some hours are necessary. Furthermore, previous studies have reported that the magnitude of PEH following a single bout of exercise was correlated with chronic changes in rest BP after a period of exercise training. 4-8 However, despite this possible relationship, some individuals present PEH (i.e., “responders”) while others do not (i.e., “non-responders”). Past studies have identified “responders” and “non-responders” in non-hypertensive. 4,8-10 and hypertensive populations. 5,6,11 This means that, in the same intervention group, some individuals may demonstrate PEH whereas others show no changes or even an increased BP response to exercise training. Indeed, results from PEH studies are generally limited to presenting the mean BP reduction responses of the training group, ignoring inter-individual variations which can lead to misinterpretation, as positive effects from a given exercise training protocol may not be fully applied for each person individually. 12 On the other hand, studies have persuasively demonstrated that citrulline (a non-essential amino acid) has a key role in the arginine-nitric oxide system, increasing nitric oxide (NO) bioavailability, 13 an important mediator of peripheral vasodilation. Thus, it is possible that PEH could be more pronounced after citrulline supplementation, especially in hypertensives, since the BP responses would be different as PEH can be caused by different mechanisms between normotensive 218