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BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Background Disturbances in the regulation of cytosolic calcium concentration have been attributed to primary hypertension, but the role of calcium-permeable transient receptor potential canonical channel 3 (TRPC3) has not yet been evaluated in primary hypertension. Methods Expression of TRPC3 was determined using in-cell Western assay. Evaluation of RNA interference for the downregulation of a specific gene in cells by small interfering RNA was performed. Measurements of cytosolic calcium were carried out using the fluorescent dye fura2. Results Expression of TRPC3 was significantly increased in monocytes from spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Transplasmamembrane calcium influx and thapsigargin-induced sustained calcium increase were significantly higher in SHR compared with WKY. In the presence of the TRP channel blocker SKF-96365 these differences were no longer observed. Specific TRPC3-knockdown by transfection of monocytes from SHR with small interfering RNA significantly reduced TRPC3 expression, trans–plasma membrane calcium influx, and thapsigargin-induced sustained calcium increase. Conclusions This study shows, for the first time, increased TRPC3 channel expression and increased TRPC3-related calcium influx in SHR.

Background Sodium-induced hypertensive cardiac hypertrophy is related to pressure and volume overload. Methods Wistar rats were exposed to low and high sodium diet for 8 weeks. Angiotensin II receptor mRNA, abundance of p38 mitogen-activated protein kinase (p38MAPK), vasoconstriction of aortic rings, and angiotensin II-induced calcium increase were investigated. Results Rats on high sodium diet showed significantly elevated blood pressure. Heart weight, AT1 receptor mRNA in cardiac and aortic tissues, and abundance of p38MAPK were significantly increased in rats on high sodium diet. Conclusions Increased AT1 receptor expression and angiotensin II-induced calcium increase are compensatory effects in sodium-induced hypertension.