Résumé
Despite sympathetic hyperactivation is considered as a key trigger of hypertension, in some obese or metabolic syndrome (MetS) subjects, such altered sympatho-vagal balance was not associated with changes in arterial blood pressure. Vascular endothelium is a potent modulator of adrenergic vascular tone, thus we aimed to determine, in a rat model of MetS, whether the endothelium and especially the classical vasodilatory eNOS-NO pathway could counteract the effect of increased sympathetic vasopressor action. After14 weeks of high fat high sucrose diet (HFS), HFS developed several features of MetS phenotype, such as increased body mass, abdominal fat accumulation, high LDL and triglycerides levels, higher fasting blood glucose and insulinemia, as well as impaired glucose and insulin tolerance compared with control rats (Ctrl) fed with standard diet. As assessed by catecholamine assay and heart rate variability analysis (HRV), HFS rats also presented increased sympathetic outflow but without consequences on skin microcirculation and arterial blood pressure. In HFS rats, vascular reactivity test revealed hyporeactivity to α1-adrenergic receptors (AR) stimulation with unchanged α 1DAR expression. This phenomenon was rather due to endothelial adaptation since endothelial removal or eNOS inhibition by L-NAME normalized adrenergic vasoconstriction in HFS rats. In addition, eNOS phosphorylation (activation site, ser1177) was increased by PE in HFS ones only. In line with this result, eNOS inhibition in-vivo also revealed higher blood pressure in HFS rats compared to Ctrl ones. In conclusion, tonic restrain of adrenergic vasopressor action by endothelium is increased in HFS rats which contribute to maintain their blood pressure in normal range.
The author hereby declares no conflict of interest