Abstract
Although dietary α-linolenic acid (ALA) or linolenic acid (LA) intake was reported to be epidemiologically associated with a lower prevalence of hypertension, recent clinical trials have yielded conflicting results. Comparable experimental evidence for the roles of these two different fatty acids is still lacking and the underlying mechanisms need to be further elucidated. Our data showed that ALA but not LA supplementation alleviated systolic blood pressure elevation and improved ACh-induced, endothelium-dependent vasodilation in both spontaneously hypertensive rats (SHRs) and AngII-induced hypertensive mice. In addition, SHRs displayed reduced vascular Sirtuin 3 (SIRT3) expression, subsequent superoxide dismutase 2 (SOD2) hyperacetylation and mitochondrial ROS overproduction, all of which were ameliorated by ALA but not LA supplementation. In primary cultured endothelial cells, ALA treatment directly inhibited SIRT3 reduction, SOD2 hyperacetylation, mitochondrial ROS overproduction and alleviated autophagic flux impairment induced by AngII plus TNFα treatment. However, these beneficial effects of ALA were completely blocked by silencing SIRT3. Restoration of autophagic flux by rapamycin also inhibited mitochondrial ROS overproduction in endothelial cells exposed to AngII plus TNFα. More interestingly, SIRT3 KO mice developed severe hypertension in response to a low dose of AngII infusion, while ALA supplementation lost its anti-hypertensive and endothelium-protective effects on these mice. Our findings suggest that ALA but not LA supplementation improves endothelial dysfunction and diminishes experimental hypertension by rescuing SIRT3 impairment to restore autophagic flux and mitochondrial redox balance in endothelial cells.