Inter-Individual Responses to Citrulline Malate Oral Supplementation on Post-Exercise Hypotension in Hypertensives: A 24-Hour Analysis / Respostas Interindividuais à Suplementação Oral de Citrulina Malato na Hipotensão Pós-Exercício em Hipertensos: Uma Análise de 24 Horas

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.

Resumo Fundamento: Estudos demonstraram de maneira persuasiva que a citrulina tem um papel fundamental no sistema arginina-óxido nítrico, aumentando a biodisponibilidade do óxido nítrico, um importante mediador da vasodilatação periférica. Objetivo: Analisar a responsividade interindividual da hipotensão pós-exercício após suplementação aguda com citrulina em hipertensos. Métodos: Quarenta hipertensos foram aleatoriamente designados para um dos quatro grupos experimentais (controle-placebo, controle-citrulina, exercício-placebo e exercício-citrulina). Eles ingeriram placebo ou citrulina malato [CM] (6 gramas). Durante a sessão de exercício, os indivíduos realizaram 40 minutos de caminhada/corrida em esteira a 60-70% da FC de reserva. Para a sessão de controle, os indivíduos permaneceram sentados em repouso por 40 minutos. A medida da pressão arterial (PA) no consultório foi realizada a cada 10 minutos até completar 60 minutos após a sessão experimental. O dispositivo ambulatorial de PA foi programado para fazer as leituras a cada 20 minutos (tempo de vigília) e a cada 30 minutos (tempo de sono) ao longo de 24 horas de monitoramento. A significância estatística foi definida como p < 0,05. Resultados: Diferentemente de outros grupos experimentais, não houve "não respondedores" no exercício/citrulina (EC) para "acordado" (PA sistólica e diastólica) e "24 horas" (PA diastólica). Os tamanhos de efeito foram mais consistentes no EC para a resposta sistólica e diastólica da PA ambulatorial. Os efeitos foram "grandes" (> 0,8) para "acordado", "dormindo", e para "24 horas" apenas no EC para a PA diastólica. Conclusão: A suplementação com CM pode aumentar os efeitos hipotensivos pós-exercício em hipertensos. Além disso, a prevalência de "não respondedores" é menor quando associada ao exercício aeróbico e à suplementação com CM.

Effect of S-methyl-l-thiocitrulline dihydrochloride on rat micturition reflex

ABSTRACT Objective: To evaluate the effect of neuronal nitric oxide synthase on the striated urethral sphincter and the urinary bladder. Materials and Methods: A coaxial catheter was implanted in the proximal urethra and another one in the bladder of female rats, which were anesthetized with subcutaneous injection of urethane. The urethral pressure with saline continuous infusion and bladder isovolumetric pressure were simultaneously recorded. Two groups of rats were formed. In group I, an intrathecal catheter was implanted on the day of the experiment at the L6-S1 level of the spinal cord; in group II, an intracerebroventricular cannula was placed 5-6 days before the experiment. Results: It was verified that the group treated with S-methyl-L-thio-citrulline, via intrathecal pathway, showed complete or partial inhibition of the urethral sphincter relaxation and total inhibition of the micturition reflexes. The urethral sphincter and the detrusor functions were recovered after L-Arginine administration. When S-methyl-L-thio-citrulline was administered via intracerebroventricular injection, there was a significant increase of urethral sphincter tonus while preserving the sphincter relaxation and the detrusor contractions, at similar levels as before the use of the drugs. Nevertheless there was normalization of the urethral tonus when L-Arginine was applied. Conclusions: The results indicate that, in female rats anaesthetized with urethane, the nNOS inhibitor administrated through the intrathecal route inhibits urethral sphincter relaxation, while intracerebroventricular injection increases the sphincter tonus, without changing bladder function. These changes were reverted by L-Arginine administration. These findings suggest that the urethral sphincter and detrusor muscle function is modulated by nitric oxide.