The hydrogen sulfide donor 4-carboxyphenyl-isothiocyanate decreases blood pressure and promotes cardioprotective effect through reduction of oxidative stress and nuclear factor kappa B/matrix metalloproteinase (MMP)-2 axis in hypertension.

AIMS: Our aim was to evaluate whether the hydrogen sulfide (H2S) donor, 4-carboxyphenyl-isothiocyanate (4-CPI), exerts cardioprotective effect in the two kidney- one clip (2K-1C) rats through oxidative stress and MMP-2 activity attenuation and compare it with the classical H2S donor, Sodium Hydrosulfide (NaHS). MATERIALS AND METHODS: Renovascular hypertension (two kidneys-one clip; 2K-1C) was surgically induced in male Wistar rats. After two weeks, normotensive (2K) and hypertensive rats were intraperitoneally treated with vehicle (0.6 % dimethyl sulfoxide), NaHS (0.24 mg/Kg/day) or with 4-CPI (0.24 mg/Kg/day), for more 4 weeks. Systolic blood pressure (SBP) was evaluated weekly by tail-cuff plethysmography. Heart function was assessed by using the Millar catheter. Cardiac hypertrophy and fibrosis were evaluated by hematoxylin and eosin, and Picrosirius Red staining, respectively. The H2S was analyzed using WSP-1 fluorimetry and the cardiac oxidative stress was measured by lucigenin chemiluminescence and Amplex Red. MMP-2 activity was measured by in-gel gelatin or in situ zymography assays. Nox1, gp91phox, MMP-2 and the phospho-p65 subunit (Serine 279) nuclear factor kappa B (NF-κB) levels were evaluated by Western blotting. KEY FINDINGS: 4-CPI reduced blood pressure in hypertensive rats, decreased cardiac remodeling and promoted cardioprotection through the enhancement of cardiac H2S levels. An attenuation of oxidative stress, with inactivation of the p65-NF-κB/MMP-2 axis was similarly observed after NaHS or 4-CPI treatment in 2K-1C hypertension. SIGNIFICANCE: H2S is a mediator that promotes cardioprotective effects and decreases blood pressure, and 4-CPI seems to be a good candidate to reverse the maladaptive remodeling and cardiac dysfunction in renovascular hypertension.

Low load strength training, associated with or without blood flow restriction increased NO production and decreased production of reactive oxygen species in rats aorta.

Studies have shown that strength training (ST) with blood flow restriction (BFR) in which low load is used (20-50% of 1 maximum voluntary contraction - MVC) can produce positive adaptations similar to ST with loads equal to or greater than 70% 1 MVC. Furthermore, recent studies have investigated the effects of STBFR on muscle adaptations, but few studies investigated the effects of STBFR on vascular function. This study aimed to evaluate the effects of the STBFR program on the vascular reactivity of the abdominal aorta of Wistar rats with femoral arteriovenous blood flow restriction. Male rats were divided into four groups: sedentary sham (S/S), sedentary with blood flow restriction (S/BFR), trained sham (T/S), and trained with blood flow restriction (T/BFR). The animals in the S/BFR and T/BFR groups underwent surgery to BFR in the femoral artery and vein. After one week, the trained groups started the ST which consisted of climbing ladder, six sets of 10 repetitions with 50% of 1 MVC assessed by maximum loaded weight (MLW) carried out for four weeks. Concentration-response curves to Acetylcholine (ACh: 10 nM - 100 µM) and Phenylephrine (PHE: 1 nM - 30 µM) were performed in aortic rings with intact endothelium. The production of nitric oxide (NO) and reactive oxygen species (ROS) in situ and the vascular remodeling marker (MMP-2) were also measured. The ST increased the strength of the T/S and T/BFR groups in MLW tests. The S/BFR group showed a 22% reduction in relaxation to acetylcholine, but exercise prevented this reduction in the T/BFR group. In animals without BFR, ST did not alter the response to acetylcholine. An increase in NO production was seen in T/S and T/BFR showed a reduction in ROS production (62% and 40%, respectively). In conclusion low load ST with BFR promotes similar vascular function responses to ST without BFR. Low load ST with and without BFR is interventions that can improve performance with similar magnitudes. Both training methods could have some benefits for vascular health due to NO production in the aorta increased in the T/S group and decreased production of reactive oxygen species in the T/BFR group.

Study of the Biomechanical and Histological Properties of the Abdominal Aorta of Diabetic Rats Exposed to Cigarette Smoke.

INTRODUCTION: In spite of the great relevance of abdominal aortic aneurysm, its etiopathogenesis is not fully understood. The biomechanical and histological study of the aortic wall may contribute to this elucidation. METHODS: Seventy-five male Wistar rats were divided into 4 groups: control (CG), smoker (SG), diabetic (DG), and diabetic + smoker (DSG). The SG and DSG rats were exposed to cigarette smoke for 30 min/day, 5 days a week. Diabetes was induced by the intravenous injection of streptozotocin. After 16 weeks, the abdominal aorta was collected for biomechanical, histological, and matrix metalloproteinase 2 (MMP-2) activity analyses. RESULTS: The valid biomechanical tests of 52 specimens were analyzed: 11 in the CG, 10 in the DG, 16 in the SG, and 15 in the DSG. The biomechanical analysis of the fragments showed no differences between the control, DG, SG, and DSG. Collagen deposition also did not present a significant difference between the studied groups. The total count of elastic fibers was higher in diabetic rats (DG and DSG) than in the SG. The inflammatory response observed in all experimental groups was significantly more intense than in the CG. Compared to the DSG, MMP-2 activity showed a significant decrease in the DG. CONCLUSIONS: Resistance and elasticity did not present a difference between the CG and the DG, SG, and DSG. Compared to the CG, the total count of elastic fibers, fragmentation of the elastic lamina, pericellular matrix deposition, and cell loss/substitution in the tunica media showed significant alterations in the aortic walls of the DG, SG, and DSG. MMP-2 activity was lower in the DG aorta than in the DSG aorta.

Long-Term Excessive Selenium Supplementation Induces Hypertension in Rats.

Selenium (Se) is an essential trace element involved in several biological pathways, naturally found in rocks, soils, and food. Even though the daily requirement of Se is achieved through a balanced diet, the use of Se supplements has been frequent. Due to the risk of toxic effects of having Se in excess, supplementation is still under debate. The aim was to evaluate the effects of long-term Se supplementation upon systolic blood pressure (SBP) and redox status of rats exposed to sodium selenite. Male Wistar rats were exposed to 2 and 6 mg/L of sodium selenite in drinking water for 85 days. SBP and body weight were evaluated weekly; oxidative stress biomarkers were measured in blood or plasma; and Se levels were assessed in blood, plasma, kidney, and liver. Se supplementation (2 and 6 mg/L) induced significant increase in the SBP in rats from the 42nd day until the end of the study. This increase on SBP was not associated with significant changes in oxidative stress biomarkers. A significant increase in Se levels was found in whole blood, kidney, and liver from both groups of rats receiving Se supplementation when compared to control. Although the exact mechanisms underlying this augment in SBP are not clear, they are potentially related to other Se biological routes besides the synthesis of selenoproteins, such as GSH-Px. Due to the negative effects upon blood pressure, precautionary measures are advised, since the selling of supplements does not require a medical prescription.