Clofibrate improves myocardial ischemia-induced damage through regulation of renin-angiotensin system and favours a pro-vasodilator profile in left ventricle.

Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment to stop ischemia-induced damage is necessary. Fibrates, have been reported to decrease inflammatory markers and to modulate the renin-angiotensin system (RAS). Our aim was to explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, rats were subdivided to receive vehicle (V) or clofibrate [100 mg/kg (C)] daily for 7 days. Blood samples and left ventricle were analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), and AT1-receptor] decreased in MI-C compared to MI-V, while [Ang-(1-7), bradykinin, ACE-2, and AT2-receptor] raised in response to clofibrate treatment. Oxidative stress markers increased in MI-V rats, a profile reverted in MI-C rats. Nitric oxide (NO) pathway (Akt, eNOS, and NO) exhibits a lower participation in MI-V, but clofibrate raised NO-pathway components and its production. MI-induced fibrosis and structural damage was also improved by clofibrate-treatment. In conclusion, clofibrate administration to 7 days MI-rats exerts an antioxidant, pro-vasodilator expression profile, and anti-fibrotic effect suggesting that PPARα activation can be considered a therapeutic target to improve cardiac condition posterior to ischemia.

Evaluation of risk factors in the development of type 2 diabetes in a Mexican population.

Type 2 diabetes (T2D), which causes many adverse effects such as endothelial dysfunction and cardiovascular disease, affects approximately 425 million people worldwide. However, about half have not yet been diagnosed. For what is recommended the use of screening tools to identify individuals at risk for T2D or in the early stages of the disease in order to impement preventive strategies or early treatment. According to a widely used survey, the FINDRISC scale, a hereditary family history of T2D (FH-T2D) is as important a risk factor as having had high glucose levels. The aim of the present study was to carry out non-probabilistic sampling in a Mexican population to evaluate key factors in the development of diabetes. The participants were divided into three groups: with and without FH-T2D and diagnosed with T2D. A comparison of the groups with and without FH-T2D revealed higher values in the former for body mass index (BMI: 24.5 vs 21.9 kg/m2), glycosylated hemoglobin [Hb1Ac: 5.775% (39 mmol/mol) vs 4.825% (29 mmol/mol)] and triglycerides (164.18 vs 68.12 mg/dL), and a lower value for the BH4/BH2 index (0.7846 vs 1.6117). These results indicate significant metabolic alterations and endothelial dysfunction for the FH-T2D group. This strongly suggests the need to screen individuals with a family history of inherited T2D based on their level of HbA1c, triglycerides and BH4.

A review of the impact of oxidative stress and some antioxidant therapies on renal damage.

An increase in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to complications during chronic kidney disease (CKD). This increase essentially derives from the impairment of natural antioxidant systems of the organism. The resulting oxidative stress produces damage to kidney tissue, especially by affecting nephrons and more generally by disrupting the function and structure of the glomerulus and interstitial tubule. This leads to a rapid decline in the condition of the patient and finally renal failure. Possible causes of kidney tissue damage are explored, as are different therapies, especially those related to the administration of antioxidants.

Role of α1D -adrenoceptors in vascular wall hypertrophy during angiotensin II-induced hypertension.

The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α1 -adrenoceptors (α1 -ARs) expression was explored. Alzet(®) minipumps filled with Ang II (200 ng kg(-1)  min(-1) ) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1 R antagonist, or with BMY 7378, a selective α1D -AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses. Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II-treated rats than in the controls, and similar effect occurred with KCl 80 mm. Responses in tail arteries were not significantly different among the different groups. Angiotensin II decreased α1D -ARs without modifying the other α1 -ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II-AT1 Rs and α1D -ARs. Angiotensin II-induced α1D -AR-mediated vascular remodeling occurs independently of hypertension. Findings identify a α1D -AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation.

Angiotensin II and 1-7 during aging in Metabolic Syndrome rats. Expression of AT1, AT2 and Mas receptors in abdominal white adipose tissue.

Renin-Angiotensin System (RAS) plays an important role in the development of Metabolic Syndrome (MS) and in aging. Angiotensin 1-7 (Ang 1-7) has opposite effects to Ang II. All of the components of RAS are expressed locally in adipose tissue and there is over-activation of adipose RAS in obesity and hypertension. We determined serum and abdominal adipose tissue Ang II and Ang 1-7 in control and MS rats during aging and the expression of AT1, AT2 and Mas in white adipose tissue. MS was induced by sucrose ingestion during 6, 12 and 18 months. During aging, an increase in body weight, abdominal fat and dyslipidemia were found but increases in aging MS rats were higher. Control and MS concentrations of serum Ang II from 6-month old rats were similar. Aging did not modify Ang II seric concentration in control rats but decreased it in MS rats. Ang II levels increased in WAT from both groups of rats. Serum and adipose tissue Ang 1-7 increased during aging in MS rats. Western blot analysis revealed that AT1 expression increased in the control group during aging while AT2 and Mas remained unchanged. In MS rats, AT1 and AT2 expression decreased significantly in aged rats. The high concentration of Ang 1-7 and adiponectin in old MS rats might be associated to an increased expression of PPAR-γ. PPAR-γ was increased in adipose tissue from MS rats. It decreased with aging in control rats and showed no changes during aging in MS rats. Ang 1-7/Mas axis was the predominant pathway in WAT from old MS animals and could represent a potential target for therapeutical strategies in the treatment of MS during aging.

Captopril avoids hypertension, the increase in plasma angiotensin II but increases angiotensin 1-7 and angiotensin II-induced perfusion pressure in isolated kidney in SHR.

We investigated captopril effects, an ACE inhibitor, on hypertension development, on Ang II and Ang-(1-7) plasma concentrations, on Ang II-induced contraction in isolated kidneys, and on kidney AT1R from spontaneously hypertensive (SHR) rats. Five weeks-old SHR and Wistar Kyoto (WKY) rats were treated with captopril at 30 mg/kg/day, in drinking water for 2 or 14 weeks. Systolic blood pressure (SBP) was measured, and isolated kidneys were tested for perfusion pressure and AT1R expression; while Ang II and Ang-(1-7) concentrations were determined in plasma. Captopril did not modify SBP in WKY rats and avoided its increase as SHR aged. Plasma Ang-II concentration was ∼4-5 folds higher in SHR rats, and captopril reduced it (P<0.05); while captopril increased Ang-(1-7) by ∼2 fold in all rat groups. Captopril increased Ang II-induced pressor response in kidneys of WKY and SHR rats, phenomenon not observed in kidneys stimulated with phenylephrine, a α1-adrenoceptor agonist. Captopril did not modify AT1R in kidney cortex and medulla among rat strains and ages. Data indicate that captopril increased Ang II-induced kidney perfusion pressure but not AT1R density in kidney of WKY and SHR rats, due to blockade of angiotensin II synthesis; however, ACE inhibitors may have other actions like activating signaling processes that could contribute to their diverse effects.

Coronary vasodilator activity of vulgarenol, a sesquiterpene isolated from Magnolia grandiflora, and its possible mechanism.

The aim of this study was to investigate the biodynamic effects of vulgarenol, a sesquiterpene isolated from Magnolia grandiflora flower petals and its possible mechanism on the Langendorff isolated and perfused heart model. Vulgarenol (5 microm) caused a statistically significant decrease in coronary vascular resistance (15.21 +/- 6.00 dyn s cm(-5) vs 36.80 +/- 5.01 dyn s cm(-5), control group), increased nitric oxide release (223.01 +/- 8.76 pmol/mL vs 61.00 +/- 12.00 pmol/mL, control group) and cyclic guanosine monophosphate accumulation in left ventricular tissue samples (142.17 +/- 8.41 pmol/mg of tissue vs 43.94 +/- 5.00 pmol/mg of tissue, control group). Pre-treatment with 3 microm gadolinium chloride hexahydrate, 100 microm N(omega)-nitro-L-arginine methyl ester hydrochloride, and 10 microm 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one significantly abolished the vulgarenol-induced coronary vascular resistance decrease, nitric oxide increased release and cGMP accumulation in left ventricular tissue samples. The results support the fact that nitric oxide and cyclic guanosine monophosphate are likely involved in the endothelium-dependent coronary vasodilation.