The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin.

Background: Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown.

Methods: A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities.

The Melatonin Derivative ITH13001 Prevents Hypertension and Cardiovascular Alterations in Angiotensin II-Infused Mice.

Inflammatory mechanisms and oxidative stress seem to contribute to the pathogenesis of hypertension. ITH13001 is a melatonin-phenyl-acrylate hybrid that moderately induces the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) and has a potent oxidant scavenging effect compared with other derivatives of its family. Here we investigated the effect of ITH13001 on hypertension and the associated cardiovascular alterations.

Sex-Dependent Impairment of Endothelium-Dependent Relaxation in Aorta of Mice with Overexpression of Hyaluronan in Tunica Media.

Diabetic macroangiopathy is characterized by increased extracellular matrix deposition, including excessive hyaluronan accumulation, vessel thickening and stiffness, and endothelial dysfunction in large arteries. We hypothesized that the overexpression of hyaluronan in the tunica media also led to endothelial cell (EC) dysfunction. To address this hypothesis, we investigated the following in the aortas of mice with excessive hyaluronan accumulation in the tunica media (HAS-2) and wild-type mice: EC dysfunction via myograph studies, nitric oxide (NO) bioavailability via diaminofluorescence, superoxide formation via dihydroethidium fluorescence, and the distances between ECs via stereological methods.

Regulation by Nrf2 of IL-1β-induced inflammatory and oxidative response in VSMC and its relationship with TLR4.

Vascular oxidative stress and inflammation play an important role in the pathogenesis of cardiovascular diseases (CVDs). The proinflammatory cytokine Interleukin-1β (IL-1β) participates in the vascular inflammatory and oxidative responses and influences vascular smooth muscle cells (VSMC) phenotype and function, as well as vascular remodelling in cardiovascular diseases. The Toll-like receptor 4 (TLR4) is also involved in the inflammatory response in cardiovascular diseases.

Vascular and Macrophage Heme Oxygenase-1 in Hypertension: A Mini-Review.

Hypertension is one predictive factor for stroke and heart ischemic disease. Nowadays, it is considered an inflammatory disease with elevated cytokine levels, oxidative stress, and infiltration of immune cells in several organs including heart, kidney, and vessels, which contribute to the hypertension-associated cardiovascular damage. Macrophages, the most abundant immune cells in tissues, have a high degree of plasticity that is manifested by polarization in different phenotypes, with the most well-known being M1 (proinflammatory) and M2 (anti-inflammatory).

Pirfenidone Is a Vasodilator: Involvement of K7 Channels in the Effect on Endothelium-Dependent Vasodilatation in Type-2 Diabetic Mice.

Endothelial cell dysfunction and fibrosis are associated with worsening of the prognosis in patients with cardiovascular disease. Pirfenidone has a direct antifibrotic effect, but vasodilatation may also contribute to the effects of pirfenidone. Therefore, in a first study we investigated the mechanisms involved in the relaxant effect of pirfenidone in rat intrapulmonary arteries and coronary arteries from normal mice.

K 1.3 channels are novel determinants of macrophage-dependent endothelial dysfunction in angiotensin II-induced hypertension in mice.

Background And Purpose: K 1.3 channels are expressed in vascular smooth muscle cells (VSMCs), where they contribute to proliferation rather than contraction and participate in vascular remodelling. K 1.

Endothelial Dysfunction and Passive Changes in the Aorta and Coronary Arteries of Diabetic db/db Mice.

Endothelial cell dysfunction and vessel stiffening are associated with a worsened prognosis in diabetic patients with cardiovascular diseases. The present study hypothesized that sex impacts endothelial dysfunction and structural changes in arteries from diabetic mice. In diabetic (db/db) and normoglycaemic (db/db+) mice, the mechanical properties were investigated in pressurized isolated left anterior descending coronary arteries and aorta segments that were subjected to tensile testing.

Pioglitazone Modulates the Vascular Contractility in Hypertension by Interference with ET-1 Pathway.

Endothelin-1 (ET-1) is an important modulator of the vascular tone and a proinflammatory molecule that contributes to the vascular damage observed in hypertension. Peroxisome-proliferator activated receptors-γ (PPARγ) agonists show cardioprotective properties by decreasing inflammatory molecules such as COX-2 and reactive oxygen species (ROS), among others. We investigated the possible modulatory effect of PPARγ activation on the vascular effects of ET-1 in hypertension.

Egg white hydrolysates improve vascular damage in obese Zucker rats by its antioxidant properties.

Metabolic Syndrome (MS) is related to increased risk of early death due to cardiovascular complications, among others. Dietary intervention has been suggested as the safest and most cost-effective alternative for treatment of those alterations in patients with MS. The aim of this study was to investigate the effects of different egg white hydrolysates (HEW1 and HEW2) in obese Zucker rats, focus on the development of cardiovascular complications.

The cessation of the long-term exposure to low doses of mercury ameliorates the increase in systolic blood pressure and vascular damage in rats.

This study aimed to verify whether a prolonged exposure to low-level mercury promotes haemodynamic disorders and studied the reversibility of this vascular damage. Rats were divided into seven groups: three control groups received saline solution (im) for 30, 60 or 90 days; two groups received HgCl (im, first dose, 4.6μg/kg, subsequent doses 0.

Hu antigen R is required for NOX-1 but not NOX-4 regulation by inflammatory stimuli in vascular smooth muscle cells.

Objective: NOX-1 and NOX-4 are key enzymes responsible for reactive oxygen species (ROS) generation in vascular smooth muscle cells (VSMC). The RNA-binding protein Hu antigen R (HuR) is implicated in posttranscriptional regulation of gene expression; however, its role regulating NOX is unknown. We investigated transcriptional and posttranscriptional mechanisms underlying angiotensin II (AngII) and IL-1β regulation of NOX-1 and NOX-4 in VSMC and their implications in cell migration.

Toll-like receptor 4 upregulation by angiotensin II contributes to hypertension and vascular dysfunction through reactive oxygen species production.

Hypertension is considered as a low-grade inflammatory disease, with adaptive immunity being an important mediator of this pathology. TLR4 may have a role in the development of several cardiovascular diseases; however, little is known about its participation in hypertension. We aimed to investigate whether TLR4 activation due to increased activity of the renin-angiotensin system (RAS) contributes to hypertension and its associated endothelial dysfunction.

Pioglitazone reduces angiotensin II-induced COX-2 expression through inhibition of ROS production and ET-1 transcription in vascular cells from spontaneously hypertensive rats.

Glitazones have anti-inflammatory properties by interfering with the transcription of proinflammatory genes, such as cyclooxygenase (COX)-2, and with ROS production, which are increased in hypertension. This study analyzed whether pioglitazone modulates COX-2 expression in hypertension by interfering with ROS and endothelin (ET)-1. In vivo, pioglitazone (2.

New roles for old pathways? A circuitous relationship between reactive oxygen species and cyclo-oxygenase in hypertension.

Elevated production of prostanoids from the constitutive (COX-1) or inducible (COX-2) cyclo-oxygenases has been involved in the alterations in vascular function, structure and mechanical properties observed in cardiovascular diseases, including hypertension. In addition, it is well known that production of ROS (reactive oxygen species) plays an important role in the impaired contractile and vasodilator responses, vascular remodelling and altered vascular mechanics of hypertension. Of particular interest is the cross-talk between NADPH oxidase and mitochondria, the main ROS sources in hypertension, which may represent a vicious feed-forward cycle of ROS production.

Exercise training and cardiometabolic diseases: focus on the vascular system.

The regular practice of physical activity is a well-recommended strategy for the prevention and treatment of several cardiovascular and metabolic diseases. Physical exercise prevents the progression of vascular diseases and reduces cardiovascular morbidity and mortality. Exercise training also ameliorates vascular changes including endothelial dysfunction and arterial remodeling and stiffness, usually present in type 2 diabetes, obesity, hypertension and metabolic syndrome.

Pioglitazone treatment increases COX-2-derived prostacyclin production and reduces oxidative stress in hypertensive rats: role in vascular function.

Background And Purpose: PPARγ agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved.

Experimental Approach: Mesenteric resistance arteries from untreated or pioglitazone-treated (2.

Peroxisome proliferator-activated receptor-γ activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress.

Aims: Hypertension is associated with increased plasma inflammatory markers such as cytokines and increased vascular cyclooxygenase-2 (COX-2) expression. The ability of peroxisome proliferator-activated receptor-γ (PPARγ) agonists to reduce oxidative stress seems to contribute to their anti-inflammatory properties. This study analyzes the effect of pioglitazone, a PPARγ agonist, on interleukin-1β-induced COX-2 expression and the role of reactive oxygen species (ROS) on this effect.

Losartan and tempol treatments normalize the increased response to hydrogen peroxide in resistance arteries from hypertensive rats.

Objective: To analyse the role of angiotensin II, via AT1 receptors, and oxidative stress in the mechanisms underlying the increased response to hydrogen peroxide (H2O2) of mesenteric resistance arteries from spontaneously hypertensive rats (SHRs).

Methods: Arteries from normotensive and SHRs untreated or treated with the AT1 receptor antagonist, losartan (15 mg/kg per day, 12 weeks), or with the superoxide dismutase analogue, tempol (1 mmol/l, 17 days), were used. Arteries were mounted in microvascular myographs for isometric tension recording; superoxide anion (O2(*-)) production was evaluated by dihydroethidium fluorescence, thromboxane A2 production by enzyme immunoassay and plasma nitrite levels by the Griess method.

Atorvastatin prevents angiotensin II-induced vascular remodeling and oxidative stress.

Angiotensin II (Ang II) modulates vasomotor tone, cell growth, and extracellular matrix deposition. This study analyzed the effect of atorvastatin in the possible alterations induced by Ang II on structure and mechanics of mesenteric resistance arteries and the signaling mechanisms involved. Wistar rats were infused with Ang II (100 ng/kg per day, SC minipumps, 2 weeks) with or without atorvastatin (5 mg/kg per day).

Ouabain treatment increases nitric oxide bioavailability and decreases superoxide anion production in cerebral vessels.

Objective: Chronic administration of ouabain induces hypertension and increases the contribution of nitric oxide to vasoconstrictor responses in peripheral arteries. The aim of this study was to analyse whether ouabain treatment alters the nitric oxide bioavailability in cerebral arteries.

Methods: Basilar arteries from control and ouabain-treated rats ( approximately 8.

Losartan reduces the increased participation of cyclooxygenase-2-derived products in vascular responses of hypertensive rats.

This study analyzes the role of angiotensin II (Ang II), via AT1) receptors, in the involvement of cyclooxygenase (COX)-2-derived prostanoids in phenylephrine responses in normotensive rats (Wistar Kyoto; WKY) and spontaneously hypertensive rats (SHR). Aorta from rats untreated or treated for 12 weeks with losartan (15 mg/kg . day) or hydralazine plus hydrochlorothiazide (44 and 9.

Vascular effects of the Mangifera indica L. extract (Vimang).

The effects of the Mangiferia indica L. (Vimang) extract, and mangiferin (a C-glucosylxanthone of Vimang) on the inducible isoforms of cyclooxygenase (cyclooxygenase-2) and nitric oxide synthase (iNOS) expression and on vasoconstrictor responses were investigated in vascular smooth muscle cells and mesenteric resistance arteries, respectively, from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Vimang (0.

Measurements of nitric oxide concentration and hyporeactivity in rat superior mesenteric artery exposed to endotoxin.

Objective: The present study was designed to relate nitric oxide (NO) concentration to changes in vascular reactivity in rat superior mesenteric arteries treated with lipopolysaccharide (LPS, 10 microg ml-1, 1-8 h).

Methods: In rat mesenteric arteries, isometric tension was recorded in wire myographs, protein expression was evaluated by Western blot and/or immunohistochemistry and NO concentration was measured by application of a NO specific electrode.

Results: Incubation with LPS (5 h) resulted in inducible NO synthase (iNOS) expression and enhanced superoxide dismutase (Cu/Zn-SOD and Mn-SOD) expression, but it did not modify endothelial NO synthase (eNOS) expression.

Hypertension alters role of iNOS, COX-2, and oxidative stress in bradykinin relaxation impairment after LPS in rat cerebral arteries.

This study was performed to investigate the role of reactive oxygen species and inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) metabolites in the lipopolysaccharide effect on bradykinin-induced relaxation in middle cerebral arteries from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). LPS exposure (10 microg/ml for 1-5 h) reduced bradykinin relaxation; this effect appeared earlier and was greater in arteries from SHR than WKY rats. LPS also reduced the relaxation to the NO donor diethylamine (DEA)-NO; however, LPS modified neither the bradykinin relaxation after inhibiting NO synthesis with N(G)-monomethyl-L-arginine (0.