L-Citrulline supplementation reduces myocardial infarct size in a rat model of sleep apnea syndrome

Abstract

Sleep apnea syndrome is characterized by intermittent hypoxia (IH), leading to an increase in blood pressure (BP), infarct size (IS), endothelial dysfunction, insulin resistance, and dyslipidemia. Insulin resistance and the metabolic syndrome associated with IH are also accompanied by an alteration in the metabolism of Arginine (Arg) [and its precursor Citrulline (Cit)]. As Arg availability directly impacts nitric oxide (NO) production, we speculate that myocardial Arg deficiency during IH may contribute to cardiovascular alterations induced by IH. Knowing that Cit is a much better precursor of Arg than Arg itself, we propose to use Cit during IH to protect against IH-induced increase in BP and IS. Four groups of rats ( n = 8), were submitted to normoxia (N) or IH [14 days (d), 8 h per d, 30 s-O 2 21%/30 s-O 2 5%] and supplemented or not with Cit (1 g.kg −1 .d −1 ). One normoxic per-feed (NPf) supplementary group was added to assess the impact of anorexia associated with IH. BW and food intake were daily measured. After 14 d, BP was measured by carotid catheterization. Hearts were perfused by the Langendorff method and submitted to global and total ischemia (30 min)-reperfusion (120 min) before measuring IS related to left ventricle area (I/V) by colorimetry and planimetry. Irrespective of diet, IH increases both systolic BP (141.3 ± 1.1 vs. 170.6 ± 5.5 mmHg in N and IH respectively, n = 4–8, P = 0.05) and I/V (27.2 ± 4.7% vs. 43.6 ± 4.5% in N and IH, respectively, n = 5–8, P < 0.05). Even if Cit increases BP under IH (170.6 ± 5.5 vs. 176.4 ± 4.4 mmHg IH and IHCit, respectively), it reduces I/V in IH groups only (43.6 ± 4.5 vs. 38.7 ± 2.9 in IH and IHCit). Under IH, Cit seems to increase the BP but decrease I/V. After completing groups, further biochemical and histological analyses will be performed to enlighten the mechanisms (NOx, NO synthase, oxidative stress…) potentially involved in the impact of Cit chronic supplementation.