Redox-Regulation of α-Globin in Vascular Physiology

Interest in the structure, function, and evolutionary relations of circulating and intracellular globins dates back more than 60 years to the first determination of the three-dimensional structure of these proteins. Non-erythrocytic globins have been implicated in circulatory control through reactions that couple nitric oxide (NO) signaling with cellular oxygen availability and redox status. Small artery endothelial cells (ECs) express free α-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe2+) α-globin to the oxidized (Fe3+) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe3+) α-globin must be stabilized and recycled to (Fe2+) α-globin to reinitiate the catalytic cycle. The molecular chaperone α-hemoglobin-stabilizing protein (AHSP) binds (Fe3+) α-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe3+) α-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome b5 reductase (CyB5R3) with cytochrome b5 type A (CyB5a) can reduce (Fe3+) α-globin in solution. Here, we examine the expression and cellular localization of eNOS, CyB5a, and CyB5R3 in mouse arterial ECs and show that α-globin can be reduced by either of two independent redox systems, CyB5R3/CyB5a and eNOS. Together, our findings provide new insights into the regulation of blood vessel contractility.

Endothelial Nitric Oxide Synthase 4a/B Polymorphism and Its Interaction with Enos G894T Variants in Type 2 Diabetic Pa-tients: Modifying the Risk of Diabetic Nephropathy

The article's abstract is not available.

Current Trends and Applications of Food Derived Antihypertensive Peptides for the Management of Cardiovascular Disease

Food derived Antihypertensive peptides is considered as a natural supplement for controlling the hypertension. Food protein not only serve as a macronutrient but also act as raw material for biosynthesis of physiologically active peptides. Food sources like milk and milk products, animal protein such as meat, chicken, fish, eggs and plant derived proteins from soy, rice, wheat, mushroom, pumpkins contain high amount of antihypertensive peptides. The food derived antihypertensive peptides has ability to supress the action of rennin and Angiotesin converting enzyme (ACE) which is mainly involved in regulation of blood pressure by RAS. The biosynthesis of endothelial nitric oxide synthase is also improved by ACE inhibitory peptides which increase the production of nitric oxide in vascular walls and encourage vasodilation. Interaction between the angiotensin II and its receptor is also inhibited by the peptides which help to reduce hypertension. This review will explore the novel sources and applications of food derived peptides for the management of hypertension.

Ferulic Acid Alleviates Atherosclerotic Plaques by Inhibiting VSMC Proliferation Through the NO/p21 Signaling pathway

The benefits and risks of inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) remain a subject of debate. In this study, we investigated the effect of ferulic acid (FA) on the proliferation and migration of VSMCs induced by platelet-derived growth factor (PDGF) and the associated mechanism and used ApoE-/- mice to study whether the effect of FA on VSMC proliferation and migration is beneficial in alleviating AS plaques. It was found that FA not only reduced blood lipid levels but also promoted the production of nitric oxide (NO) by MOVAS cells through the endothelial nitric oxide synthase (eNOS) pathway, inhibited the migration and proliferation of VSMCs induced by PDGF, promoted the expression of p21 in VSMCs, and exerted a therapeutic effect against AS.

Synthetic Pyridoindole and Rutin Affect Upregulation of Endothelial Nitric Oxide Synthase and Heart Function in Rats Fed a High-Fat-Fructose Diet

Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-κB) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-κB expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.

The role of ENOS polymorphism (C774T) in the progression of acute peritonitis and the formation of complications

In order to determine the role of ENOS (C774T) gene polymorphism in the progression of acute peritonitis and the formation of complications, a clinical and biochemical study of 40 patients with acute peritonitis was conducted. As a result of the study, it was proved that the early period of acute peritonitis is characterized by the development of endogenous intoxication, intensification of oxidative phenomena, hypercoagulation of the homeostasis system and inhibition of fibrinolysis, and in patients with acute peritonitis, carriers of the pathological TT genotype of the endothelial nitric oxide synthase gene, more pronounced deviations of homeostatic parameters are observed. Key words: acute peritonitis, genotype, DNA diagnostics, genetic testing of genotypes.

Food Restriction Augmented Alpha1 Adrenergic Mediated Contraction in Mesenteric Arteries

Food restriction (FR) enhances the sensitivity to cardiopulmonary reflexes and alpha1 adrenoreceptors in the female, despite hypotension. The effect of male FR on cardiopulmonary and systemic vascular function is not well understood. This study examines the effects of FR on cardiopulmonary, isolated mesenteric arterial function and potential underlying mechanisms. We hypothesized that FR decreased eNOS activity in mesenteric arteries. Male Sprague Dawley (SD) rats were randomly divided into three groups: (1) control (n=30), (2) 20 percent of food reduction (FR20, n=30), and (3) 40 percent of food reduction (FR40, n=30) for five weeks. Non-invasive blood pressure was measured twice a week. Pulmonary arterial pressure (PAP) was measured using isolated/perfused lungs in rats. The isolated vascular reactivity was assessed in double-wire myograph. After five weeks, food restricted rats exhibited a lower mean arterial pressure and heart rate, however, only FR40 groups exhibited statistically significant differences. The basal tone of PAP and various vasoconstrictors did not show significant differences in pulmonary circulation between each group. We observed that food restriction were enhanced the sensitivity (EC50) in response to α1-adrenoreceptors (phenylephrine, PhE)-induced vasoconstriction, but not to serotonin, U46619, and high K+ in the mesenteric arteries. FR reduced endothelium-dependent relaxation via decreased function of endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) pathway in the mesenteric arteries. PhE-mediated vasoconstriction in mesenteric arteries was eliminated in the presence of eNOS inhibitor (L-NAME). In addition, incubation with NOX2/4 inhibitors (apocynin, GKT137831, VAS2870) and reactive oxygen species (ROS) scavenger inhibitor (Tiron) were eliminated the differences of PhE-mediated vasoconstriction but not to cyclooxygenase inhibitor (indomethacin) in the mesenteric artery. Augmentation of alpha1 adrenergic mediated contraction via inhibition of eNOS-NO pathway by increased activation of ROS through NOX2/4 in response to FR. Reduced eNOS-NO signaling might be a pathophysiological counterbalance to prevent hypovolemic shock in response to FR.