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Título

Effects of hydroxychloroquine on blood pressure control in sleep apnea

Introdução

Obstructive sleep apnea (OSA) is recognized as independently associated with high blood pressure. Protocols of chronic intermittent hypoxia (CIH) increase blood pressure (BP) in animal models. Hypertension has been linked to inflammation. Hydroxychloroquine (HCQ) has been proven to exert anti-inflammatory effects through down-regulation of pro-inflammatory cytokines.

Objetivo

We hypothesized that CIH simulating sleep apnea causes hypertension via inflammation-mediated mechanisms and that hypertension could be inhibited by the anti-inflammatory action of HCQ.

Métodos

Seventeen male 12-week-old Wistar rats were submitted to telemetry sensor implantation surgery (DSI®, USA) for continuous BP verification. After surgical recovery, they underwent 14-day CIH protocol with either injection of 35mg/kg/day of HCQ diluted in saline (Sigma-Aldrich, USA) (CIH+HCQ group, n=5) or saline vehicle (CIH group, n=6) or sham hypoxia with saline vehicle injection (sham group, n=6). The hypoxia protocol was performed by introducing nitrogen into the cages reducing the oxygen fraction from 21% to 7±1%. The rats underwent CIH daily during 8 hours, simulating an apnea/hypopnea index of 51/h. The BP recordings were performed in the morning and in the afternoon. Averages of individual BP values were calculated for each day. For the present analysis, only mean arterial pressure (MAP) data were used. P values were obtained from generalized estimating equations with Bonferroni’s correction for multiple comparisons.

Resultados

No baseline MAP difference was seen (day-1: Sham, 123±2mmHg; CIH, 114±6mmHg; CIH+HCQ, 117±4mmHg), but at 14-day follow-up (day-14: Sham, 105±5mmHg; CIH, 121±3mmHg; CIH+HCQ, 115±2mmHg) a significant difference existed between sham and CIH groups (p=0.01). The HCQ group effect on delta MAP from day-1 to day-14 exposure against CIH and sham groups showed statically significant time × group interaction (p<0.001).

Conclusões

The CIH model is capable of increasing significantly MAP, confirming previous reports of the OSA role on the pathogenesis of high blood pressure. Our data suggests a potential inflammatory pathway in the OSA-hypertension relationship, which is mitigated by the use of HCQ. Studies in humans are needed to assess the effect of HCQ as adjunctive therapy in OSA.

Palavras-chave

intermittent hypoxia, sleep apnea, hydroxychloroquine

Área

Área Básica

Instituições

Faculdade de Desenvolvimento do Rio Grande do Sul - Rio Grande do Sul - Brasil, Hospital de Clínicas de Porto Alegre - Rio Grande do Sul - Brasil, Universidade Federal do Rio Grande do Sul - Rio Grande do Sul - Brasil

Autores

Chaiane Facco Piccin, Silvia Guaresi, Nicole do Nascimento, Marcela Elisa Pearson, Matheus Abreu Azeredo, Pedro Truccolo Chiarello, Jéssica Cristina de Cezaro, Lauren Sezerá Costa , Daniela Campagnol, Denis Martinez