Susana Jerez

Alcohol Drinking and Blood Pressure Among Adolescents

The purpose of this study was to evaluate alcohol consumption among adolescents from Tucuman, Argentina, and to determine its possible relationship with increased levels of blood pressure. Three hundred fifty-six students aged 13-18 included in the study were asked to answer questionnaires anonymously. Two blood pressures measures were then taken. Differences between both sexes were found in quantity and frequency of alcohol consumption. Enjoyment was determined to be the main reason for drinking. There was an association between frequency and alcohol-related problems, and smoking habits. There were also differences in blood pressure among males and females. A weak, but significant, relationship between quantity/frequency index and diastolic blood pressure was found. A greater prevalence of hypertension in male heavy drinkers was noted as well. Because this addiction implies multiple social problems and it also accounts for a hypertension risk factor, the importance of aiming at developing prevention strategies for alcohol abuse among adolescents is stressed.

The role of oxidative stress in alterations of hematological parameters and inflammatory markers induced by early hypercholesterolemia.

AIMS The investigation of the effects of a high cholesterol diet (HD) for a short-time period on hematological parameters and the potential role of oxidative stress and inflammation markers. MAIN METHODS Rabbits were fed either a control diet or a diet containing 1% cholesterol (HD) for 5-6 weeks. The plasma lipid levels, C reactive protein (CRP), total red blood cells (RBC), total white blood cells (WBC), platelet count, packed cell volume (PCV) and leukocyte formula were determined. Oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS), total glutathione and GSH serum level measurements. The osmotic fragility and the membrane fluidity of erythrocytes were determined. The levels of total cholesterol and TBARS were also measured in the erythrocyte membrane suspension. KEY FINDINGS A decrease in the RBC and PCV was observed in rabbits fed on HD. The membrane rigidity and osmotic fragility were increased, and the morphological changes caused by the HD and TBARS levels in the erythrocyte membrane may account for this phenomenon. The inflammatory markers as the CRP levels, the platelet count, the WBC and the neutrophils were increased. The TBARS and GSH levels in the serum were increased and decreased, respectively. SIGNIFICANCE This study shows that feeding rabbits an HD for a short time induces hematological alterations, disturbances in the oxidant-antioxidant balance and an increase of inflammatory markers. These findings support the importance of the early correction or prevention of high cholesterol levels to disrupt the process leading to the development of cardiovascular diseases.

Angiotensin-(1-7) increases osmotic water permeability in isolated toad skin

Angiotensin-(1-7) (Ang-(1-7)) increased osmotic water permeability in the isolated toad skin, a tissue with functional properties similar to those of the distal mammalian nephron. Concentrations of 0.1 to 10 microM were effective, with a peak at 20 min. This effect was similar in magnitude to that of frog skin angiotensin II (Ang II) and oxytocin but lower than that of human Ang II and arginine-vasotocin. The AT2 angiotensin receptor antagonist PD 123319 (1.0 microM) fully inhibited the response to 0.1 microM Ang-(1-7) but had no effect on the response to Ang II at the same concentration. The specific receptor antagonist of Ang-(1-7), A-779, was ineffective in blocking the response to Ang-(1-7) and to frog skin Ang II. The AT1 receptor subtype antagonist losartan, which blocked the response to frog skin Ang II, was ineffective in blocking the response to Ang-(1-7). The present results support the view of an antidiuretic action of Ang-(1-7) in the mammalian nephron.

Hypercholesterolemia modifies angiotensin II desensitisation and cross talk between α1-adrenoceptor and angiotensin AT1 receptor in rabbit aorta

This study characterised the effect of a hypercholesterolemic diet on the interactions of hormone receptors in the rabbit aorta, both in homologous desensitisation to angiotensin II and cross talk between alpha(1)-adrenoceptors and angiotensin AT(1) receptors. Rabbits were fed either a normal chow or a diet containing 1% cholesterol for 6-7-weeks. Isometric contractions were measured in endothelium-intact or endothelium-removed aortic rings from control and hypercholesterolemic rabbits. Concentration response curves to angiotensin II or noradrenaline incubated with or without prazosin or losartan were performed. In another group, the resting potential was recorded at baseline and following angiotensin II or noradrenaline stimulation. Rabbits fed a hypercholesterolemic diet showed higher plasma levels of total cholesterol and LDL-cholesterol and impaired relaxation to acetylcholine. Homologous desensitisation to angiotensin II was found in endothelium-intact but not in endothelium-removed arteries. Cross talk between alpha(1)-adrenoceptors and angiotensin AT(1) receptors was modified with respect to physiological conditions. In control rabbits, angiotensin II desensitised the noradrenaline response but noradrenaline did not modify the angiotensin II-response. However, in hypercholesterolemic rabbits, angiotensin II sensitised the noradrenaline-response and noradrenaline desensitised the angiotensin II-response. Furthermore, the resting potential remains hyperpolarised after noradrenaline stimulation in hypercholesterolemic rabbits. Modifications in homologous desensitisation to angiotensin II and cross talk between alpha(1)-adrenoceptors and angiotensin AT(1) receptors suggest that hypercholesterolemia induces early tissue dysfunction by altering endothelial and smooth muscle cell regulatory properties. This may be one of the mechanisms by which hypercholesterolemia could be involved in the onset and progression of chronic vascular diseases such as hypertension and arteriosclerosis.

Beneficial effects of hydroalcoholic extract and flavonoids from Zuccagnia punctata in a rabbit model of vascular dysfunction induced by high cholesterol diet

This study evaluated the effects of a Zuccagnia punctata standardized hydroalcoholic extract (ZpE) and three of its major flavonoids [2′,4′-dihydroxychalcone (DHC), 7-hydroxyflavanone (HF) and 3,7-dihydroxyflavone (DHF)] on the vascular reactivity of aortic rings with endothelial dysfunction induced by feeding rabbits on a high cholesterol diet. Rabbits were fed with either normal chow or a diet containing 1% cholesterol for 5–6 weeks. Isometric contractions were measured. Concentration response curves to ZpE (range from 4 × 10−2 to 4 × 10 µg gallic acid equivalent/ml), DHC, DHF or HF (range from 10−9 to 10−4 M) showed concentration-dependent relaxation of arteries pre-contracted with phenylephrine. ZpE (4 × 10−2, 4 × 10−1 and 4 µg gallic acid equivalent/ml), HF (10−9, 10−7, 10−5 M), DHC (10−9 M) and DHF (10−9 M) added to the bath improved acetylcholine affinity. Pre-treatment of arteries with ZpE (4 × 10−2 µg gallic acid equivalent/ml) and DHC (10−9 M) reduced phenylephrine-induced contraction. Incubation with the higher dose of ZpE (4 µg gallic acid equivalent/ml) reduced the angiotensin II-maximal contraction (Cmax) acting as a non-competitive antagonist, while DHC and DHF (10−5 M) caused a non-parallel rightward of the angiotensin II-concentration response curves and reduced the Cmax acting as mixed antagonists. ZpE (4 × 10−2 µg gallic acid equivalent/ml), DHC and DHF (10−9 M) caused a rightward displacement of angiotensin II-concentration response curves acting as competitive antagonists. In conclusion, the present study demonstrated that a ZpE and its major flavonoids had beneficial effects in arteries with vascular dysfunction induced by hypercholesterolemia. Therefore its use as herbal medicine to prevent cardiovascular risks factors may be promising.

17-Octadecynoic acid improves contractile response to angiotensin II by releasing vasocontrictor prostaglandins.

The present study investigated the role of CYP-enzymes in the modulation of vasoconstrictor responses to angiotensin II in rabbit aortae. In arteries with the endothelium-intact (E+) the CYP-inhibitor, 17-octadecynoic acid (17 ODYA), increased the efficacy to angiotensin II (17-ODYA-effect) as well as simultaneous incubation with miconazole (epoxygenase-inhibitor) and CAY 10434 (ω-hydroxylase-inhibitor). The removal of endothelium (E-) caused potentiation of the 17 ODYA-effect. Therefore, endothelium-dependent and -independent mechanisms would be involved. 17-ODYA and miconazole reduced Ach-relaxation. Indomethacin blocked the 17-ODYA-effect in E+ and E- arteries but blunted the response to angiotensin II only in E+ arteries. NS 398 (cyclooxygenase-2-inhibitor) blocked the 17-ODYA-effect and reduced angiotensin II affinity as well as SQ 29548 (thromboxane-prostanoid (TP) receptor-inhibitor). In E- arteries, CAY 10434 enhanced angiotensin II response as well as 17-ODYA. SC 560 (cyclooxygenase-1-inhibitor) and NS 398 partially blocked the 17-ODYA-effect. In conclusion, 17-ODYA induced endothelial dysfunction by inhibiting CYP-epoxygenase and thus improves vasoconstrictor cyclooxygenase-2 metabolites release acting through TP receptors. The endothelium-independent mechanism of 17-ODYA-effect may involve increase of vasoconstrictor cyclooxygenase-metabolites induced by prostaglandin-ω-hydroxylase-inhibition.

High fat diet-induced metabolically obese and normal weight rabbit model shows early vascular dysfunction: mechanisms involved

BackgroundObesity contributes significantly to the development and evolution of cardiovascular disease (CVD) which is believed to be mediated by oxidative stress, inflammation and endothelial dysfunction. However, the vascular health of metabolically obese and normal weight (MONW) individuals is not completely comprehended.ObjectivesThe purpose of our study was to evaluate vascular function on the basis of a high fat diet (HFD)-MONW rabbit model.SubjectsTwenty four male rabbits were randomly assigned to receive either a regular diet (CD, n = 12) or a high-fat diet (18% extra fat on the regular diet, HFD, n = 12) for 6 weeks.ResultsBody weight, TBARS and gluthathione serum levels were similar between the groups; fasting glucose, triglycerides, C reactive protein (CRP), visceral adipose tissue (VAT), triglyceride-glucose index (TyG index) were higher in the HFD group. Compared to CD, the HFD rabbits had glucose intolerance and lower HDL-cholesterol and plasma nitrites levels. Thoracic aortic rings from HFD rabbits exhibited: (a) a reduced acetylcholine-induced vasorelaxation; (b) a greater contractile response to norepinephrine and KCl; (c) an improved angiotensin II-sensibility. The HFD-effect on acetylcholine-response was reversed by the cyclooxygenase-2 (COX-2) inhibitor (NS398) and the cyclooxygenase-1 inhibitor (SC560), and the HFD-effect on angiotensin II was reversed by NS398 and the TP receptor blocker (SQ29538). Immunohistochemistry and western blot studies showed COX-2 expression only in arteries from HFD rabbits.ConclusionsOur study shows a positive pro-inflammatory status of HFD-induced MONW characterized by raised COX-2 expression, increase of the CRP levels, reduction of NO release and oxidative stress-controlled conditions in an early stage of metabolic alterations characteristic of metabolic syndrome. Endothelial dysfunction and increased vascular reactivity in MONW individuals may be biomarkers of early vascular injury. Therefore, the metabolic changes induced by HFD even in normal weight individuals may be associated to functional alterations of blood vessels.