Uncoupling Protein 2 Ablation Exacerbates High-Salt Intake-Induced Vascular Dysfunction

Abstract

Salt-induced vascular dysfunction in which underlying mechanisms involve reactive oxygen species (ROS)-mediated reduction of nitric oxide (NO) bioavailability has been well documented. Uncoupling protein 2 (UCP2) has been implicated in the vascular protection, specifically by decreasing ROS production. However, it is unclear how UCP2 affects vascular function in salt-loaded mice. UCP2-deficient (UCP2(-/-)) and wild-type (WT) mice were placed on either a normal-salt (NS, 0.5%) or a high-salt (HS, 8%) diet for 24 weeks. Blood pressure (BP), mesenteric arterial reactivity, superoxide production, and NO bioavailability in the intact vessels were measured in each group. UCP2(-/-) mice on a HS diet had a higher BP than those on a NS diet (P < 0.01). However, BP in WT mice was not different between the NS and HS diet group. Phenylephrine (PE)-induced contraction was enhanced while acetylcholine (ACh)-elicited relaxation was impaired in mesenteric resistance arteries from the HS diet-fed WT mice. Importantly, the enhanced contraction and impaired relaxation were both further exacerbated in UCP2(-/-) mice. Similarly, the HS diet led to a moderate increase in superoxide production and a comparable decrease in NO availability in both aortas and mesenteric resistance vessels, and these effects were also remarkably enhanced in UCP2(-/-) mice. These findings suggest that UCP2 plays an important role in preventing salt-sensitive hypertension, which may be achieved by suppressing superoxide production and reserving NO bioavailability in blood vessels.