Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats

Background: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. Objective: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. Methods: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. Results: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. Conclusion: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations. (Arq Bras Cardiol 2012;99(4):907-914)

Alterations in vasoconstrictor responses to the endothelium-derived contracting factor uridine adenosine tetraphosphate are region specific in DOCA-salt hypertensive rats

Uridine adenosine tetraphosphate (Up(4)A) has been recently identified as a novel and potent endothelium-derived contracting factor and contains both purine and pyrimidine moieties, which activate purinergic P2X and P2Y receptors. The present study was designed to compare contractile responses to Up(4)A and other nucleotides such as ATP (P2X/P2Y agonist), UTP (P2Y(2)/P2Y(4) agonist), UDP (P2Y(6) agonist), and alpha,beta-methylene ATP (P2X(1) agonist) in different vascular regions [thoracic aorta, basilar, small mesenteric, and femoral arteries] from deoxycorticosterone acetate-salt (DOCA-salt) and control rats. In DOCA-salt rats [vs. control uninephrectomized (Uni) rats]: (1) in thoracic aorta, Up(4)A-, ATP-, and UP-induced contractions were unchanged; (2) in basilar artery, Up(4)A-, ATP-, UTP- and UDP-induced contractions were increased, and expression for P2X(1), but not P2Y(2) or P2Y(6) was decreased; (3) in small mesenteric artery, Up(4)A-induced contraction was decreased and UDP-induced contraction was increased; expression of P2Y(2) and P2X(1) was decreased whereas P2Y(6) expression was increased; (4) in femoral artery, Up(4)A-. UTP-, and UDP-induced contractions were increased, but expression of P2Y(2), P2Y(6) and P2X(1) was unchanged. The alpha,beta-methylene ATP-induced contraction was bell-shaped and the maximal contraction was reached at a lower concentration in basilar and mesenteric arteries from Uni rats, compared to arteries from DOCA-salt rats. These results suggest that Up(4)A-induced contraction is heterogenously affected among various vascular beds in arterial hypertension. P2Y receptor activation may contribute to enhancement of Up(4)A-induced contraction in basilar and femoral arteries. These changes in vascular reactivity to Up(4)A may be adaptive to the vascular alterations produced by hypertension. (C) 2011 Elsevier Ltd. All rights reserved.

No effect of creatine supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats

Background: Exacerbated oxidative stress is thought to be a mediator of arterial hypertension. It has been postulated that creatine (Cr) could act as an antioxidant agent preventing increased oxidative stress. The aim of this study was to investigate the effects of nine weeks of Cr or placebo supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR). Findings: Lipid hydroperoxidation, one important oxidative stress marker, remained unchanged in the coronary artery (Cr: 12.6 +/- 1.5 vs. Pl: 12.2 +/- 1.7 nmol.mg(-1); p = 0.87), heart (Cr: 11.5 +/- 1.8 vs. Pl: 14.6 +/- 1.1 nmol.mg(-1); p = 0.15), plasma (Cr: 67.7 +/- 9.1 vs. Pl: 56.0 +/- 3.2 nmol.mg(-1); p = 0.19), plantaris (Cr: 10.0 +/- 0.8 vs. Pl: 9.0 +/- 0.8 nmol.mg(-1); p = 0.40), and EDL muscle (Cr: 14.9 +/- 1.4 vs. Pl: 17.2 +/- 1.5 nmol.mg(-1); p = 0.30). Additionally, Cr supplementation affected neither arterial blood pressure nor heart structure in SHR (p > 0.05). Conclusions: Using a well-known experimental model of systemic arterial hypertension, this study did not confirm the possible therapeutic effects of Cr supplementation on oxidative stress and cardiovascular dysfunction associated with arterial hypertension.

Genetic mapping of a new heart rate QTL on chromosome 8 of spontaneously hypertensive rats

Abstract Background Tachycardia is commonly observed in hypertensive patients, predominantly mediated by regulatory mechanisms integrated within the autonomic nervous system. The genetic loci and genes associated with increased heart rate in hypertension, however, have not yet been identified. Methods An F2 intercross of Spontaneously Hypertensive Rats (SHR) × Brown Norway (BN) linkage analysis of quantitative trait loci mapping was utilized to identify candidate genes associated with an increased heart rate in arterial hypertension. Results Basal heart rate in SHR was higher compared to that of normotensive BN rats (365 ± 3 vs. 314 ± 6 bpm, p < 0.05 for SHR and BN, respectively). A total genome scan identified one quantitative trait locus in a 6.78 cM interval on rat chromosome 8 (8q22–q24) that was responsible for elevated heart rate. This interval contained 241 genes, of which 65 are known genes. Conclusion Our data suggest that an influential genetic region located on the rat chromosome 8 contributes to the regulation of heart rate. Candidate genes that have previously been associated with tachycardia and/or hypertension were found within this QTL, strengthening our hypothesis that these genes are, potentially, associated with the increase in heart rate in a hypertension rat model.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

Abstract Background Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70–80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx-) were measured. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. Results High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NOx- levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. Conclusion The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation.

Effect of 6-months of physical exercise on the nitrate/nitrite levels in hypertensive postmenopausal women

Abstract Background Evidences have showed that the incidence of arterial hypertension is greater in postmenopausal women as compared to premenopausal. Physical inactivity has been implicated as a major contributor to weight gain and abdominal obesity in postmenopausal women and the incidence of cardiovascular disease increases dramatically after menopause. Additionally, more women than men die each year of coronary heart disease and are twice as likely as men to die within the first year after a heart attack. A healthy lifestyle has been strongly associated with the regular physical activity and evidences have shown that physically active subjects have more longevity with reduction of morbidity and mortality. Nitric oxide (NO) produced by endothelial cells has been implicated in this beneficial effect with improvement of vascular relaxing and reduction in blood pressure in both laboratory animals and human. Although the effect of exercise training in the human cardiovascular system has been largely studied, the majority of these studies were predominantly conducted in men or young volunteers. Therefore, the aim of this work was to investigate the effects of 6 months of dynamic exercise training (ET) on blood pressure and plasma nitrate/nitrite concentration (NOx-) in hypertensive postmenopausal women. Methods Eleven volunteers were submitted to the ET consisting in 3 days a week, each session of 60 minutes during 6 months at moderate intensity (50% of heart rate reserve). Anthropometric parameters, blood pressure, NOx- concentration were measured at initial time and after ET. Results A significant reduction in both systolic and diastolic blood pressure values was seen after ET which was accompanied by markedly increase of NOx- levels (basal: 10 ± 0.9; ET: 16 ± 2 μM). Total cholesterol was significantly reduced (basal: 220 ± 38 and ET: 178 ± 22 mg/dl), whereas triglycerides levels were not modified after ET (basal: 141 ± 89 and ET: 147 ± 8 mg/dl). Conclusion Our study shows that changing in lifestyle promotes reduction of arterial pressure which was accompanied by increase in nitrite/nitrate concentration. Therefore, 6-months of exercise training are an important approach in management arterial hypertension and play a protective effect in postmenopausal women.

Echocardiographic and hemodynamic determinants of right coronary artery flow reserve and phasic flow pattern in advanced non-ischemic cardiomyopathy

Abstract Background In patients with advanced non-ischemic cardiomyopathy (NIC), right-sided cardiac disturbances has prognostic implications. Right coronary artery (RCA) flow pattern and flow reserve (CFR) are not well known in this setting. The purpose of this study was to assess, in human advanced NIC, the RCA phasic flow pattern and CFR, also under right-sided cardiac disturbances, and compare with left coronary circulation. As well as to investigate any correlation between the cardiac structural, mechanical and hemodynamic parameters with RCA phasic flow pattern or CFR. Methods Twenty four patients with dilated severe NIC were evaluated non-invasively, even by echocardiography, and also by cardiac catheterization, inclusive with Swan-Ganz catheter. Intracoronary Doppler (Flowire) data was obtained in RCA and left anterior descendent coronary artery (LAD) before and after adenosine. Resting RCA phasic pattern (diastolic/systolic) was compared between subgroups with and without pulmonary hypertension, and with and without right ventricular (RV) dysfunction; and also with LAD. RCA-CFR was compared with LAD, as well as in those subgroups. Pearson's correlation analysis was accomplished among echocardiographic (including LV fractional shortening, mass index, end systolic wall stress) more hemodynamic parameters with RCA phasic flow pattern or RCA-CFR. Results LV fractional shortening and end diastolic diameter were 15.3 ± 3.5 % and 69.4 ± 12.2 mm. Resting RCA phasic pattern had no difference comparing subgroups with vs. without pulmonary hypertension (1.45 vs. 1.29, p = NS) either with vs. without RV dysfunction (1.47 vs. 1.23, p = NS); RCA vs. LAD was 1.35 vs. 2.85 (p < 0.001). It had no significant correlation among any cardiac mechanical or hemodynamic parameter with RCA-CFR or RCA flow pattern. RCA-CFR had no difference compared with LAD (3.38 vs. 3.34, p = NS), as well as in pulmonary hypertension (3.09 vs. 3.10, p = NS) either in RV dysfunction (3.06 vs. 3.22, p = NS) subgroups. Conclusion In patients with chronic advanced NIC, RCA phasic flow pattern has a mild diastolic predominance, less marked than in LAD, with no effects from pulmonary artery hypertension or RV dysfunction. There is no significant correlation between any cardiac mechanical-structural or hemodynamic parameter with RCA-CFR or RCA phasic flow pattern. RCA flow reserve is still similar to LAD, independently of those right-sided cardiac disturbances.

Consenso 2012 da Sociedade Brasileira de Reumatologia sobre o manejo de comorbidades em pacientes com artrite reumatoide

OBJETIVO: Elaborar recomendações da Comissão de Artrite Reumatoide da Sociedade Brasileira de Reumatologia (SBR) para o manuseio das comorbidades em artrite reumatoide (AR). MÉTODOS: Revisão da literatura e opinião de especialistas da Comissão de AR da SBR. RESULTADOS E CONCLUSÕES: Recomendações: 1) Diagnosticar e tratar precoce e adequadamente as comorbidades; 2) O tratamento específico da AR deve ser adaptado às comorbidades; 3) Inibidores da enzima conversora da angiotensina (IECA) ou bloqueadores dos receptores de angiotensina II (BRA) são preferidos no tratamento da hipertensão arterial sistêmica; 4) Em pacientes com AR e diabetes mellitus, deve-se evitar o uso contínuo de dose cumulativa alta de corticoides; 5) Sugere-se o uso de estatinas para manter níveis de LDL menor que 100 mg/dL e índice aterosclerótico menor que 3,5 em pacientes com AR e comorbidades; 6) A síndrome metabólica deve ser tratada; 7) Recomenda-se a realização de exames para a investigação de aterosclerose subclínica; 8) Maior vigilância para um diagnóstico precoce de neoplasia oculta; 9) Medidas de prevenção para trombose venosa são sugeridas; 10) Recomenda-se a realização de densitometria óssea em pacientes com AR acima de 50 anos, e naqueles com idade menor com corticoide maior que 7,5 mg por mais de três meses; 11) Pacientes com AR e osteoporose devem evitar quedas, e devem ser aconselhados a aumentarem a ingestão de cálcio, aumentarem a exposição solar e fazerem atividade física; 12) Suplementação de cálcio e vitamina D é sugerida.Autilização de bisfosfonatos é sugerida para pacientes com escore T menor que -2,5 na densidade mineral óssea; 13) Recomenda-se equipe multidisciplinar, com participação ativa do médico reumatologista no tratamento das comorbidades.

Effects of different tidal volumes in pulmonary and extrapulmonary lung injury with or without intraabdominal hypertension

We hypothesized that: (1) intraabdominal hypertension increases pulmonary inflammatory and fibrogenic responses in acute lung injury (ALI); (2) in the presence of intraabdominal hypertension, higher tidal volume reduces lung damage in extrapulmonary ALI, but not in pulmonary ALI. Wistar rats were randomly allocated to receive Escherichia coli lipopolysaccharide intratracheally (pulmonary ALI) or intraperitoneally (extrapulmonary ALI). After 24 h, animals were randomized into subgroups without or with intraabdominal hypertension (15 mmHg) and ventilated with positive end expiratory pressure = 5 cmH(2)O and tidal volume of 6 or 10 ml/kg during 1 h. Lung and chest wall mechanics, arterial blood gases, lung and distal organ histology, and interleukin (IL)-1 beta, IL-6, caspase-3 and type III procollagen (PCIII) mRNA expressions in lung tissue were analyzed. With intraabdominal hypertension, (1) chest-wall static elastance increased, and PCIII, IL-1 beta, IL-6, and caspase-3 expressions were more pronounced than in animals with normal intraabdominal pressure in both ALI groups; (2) in extrapulmonary ALI, higher tidal volume was associated with decreased atelectasis, and lower IL-6 and caspase-3 expressions; (3) in pulmonary ALI, higher tidal volume led to higher IL-6 expression; and (4) in pulmonary ALI, liver, kidney, and villi cell apoptosis was increased, but not affected by tidal volume. Intraabdominal hypertension increased inflammation and fibrogenesis in the lung independent of ALI etiology. In extrapulmonary ALI associated with intraabdominal hypertension, higher tidal volume improved lung morphometry with lower inflammation in lung tissue. Conversely, in pulmonary ALI associated with intraabdominal hypertension, higher tidal volume increased IL-6 expression.

Antiphospholipid syndrome plus rheumatic fever: a higher risk factor for stroke?

To compare clinical and laboratory findings between patients with primary antiphospholipid syndrome (PAPS) versus secondary APS due to rheumatic fever (APS-RF) (according to Jones criteria). Seventy-three APS patients (Sapporo criteria) were enrolled, and demographic, clinical, and laboratory data were collected. Exclusion criteria were heart congenital abnormalities and previous infectious endocarditis. Patients were divided into two groups: PAPS (n = 68) and APS-RF (n = 5). The mean current age, disease duration, frequencies of female gender, and Caucasian race were similar in APS-RF and PAPS patients (P > 0.05). Remarkably, the frequency of stroke was significantly higher in APS-RF compared to PAPS patients (80% vs. 25%, P = 0.02). Of note, echocardiogram of these patients did not show intracardiac thrombus. No significant differences were found in peripheral thromboembolic events (P = 1.0), pulmonary thromboembolism (P = 1.0), miscarriage (P = 0.16), thrombocytopenia (P = 0.36), arterial events (P = 0.58), and thrombosis of small vessels (P = 1.0). There were no differences in the frequencies of comorbidities such as diabetes mellitus, hypertension, smoking, and hyperlipidemia in both groups (P > 0.05). The frequencies of lupus anticoagulant, IgG, and IgM anticardiolipin were similar in two groups. APS patients associated with rheumatic fever without infective endocarditis may imply a high stroke risk as compared with PAPS, and future studies are needed to confirm this finding.

Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in Experimental Ischemic Stroke

Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23 +/- 9%) than animals with left dominance (7 +/- 5%, P<0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation.

Ethanol Consumption Alters the Expression and Reactivity of Adrenomedullin in the Rat Mesenteric Arterial Bed

Aims: Adrenomedullin (AM) is a peptide that displays cardiovascular protective activity. We investigated the effects of chronic ethanol consumption on arterial blood pressure, vascular reactivity to AM and the expression of AM system components in the rat mesenteric arterial bed (MAB). Methods: Male Wistar rats were treated with ethanol (20% vol/vol) for 6 weeks. Systolic, diastolic and mean arterial blood pressure were monitored in conscious rats. Vascular reactivity experiments were performed on isolated rat MAB. Matrix metalloproteinase-2 (MMP-2) levels were determined by gelatin zymography. Nitrite and nitrate generation were measured by chemiluminescence. Protein and mRNA levels of pre-pro-AM, CRLR (calcitonin receptor-like receptor) and RAMP1, 2 and 3 (receptor activity-modifying proteins) were assessed by western blot and quantitative real-time polymerase chain reaction, respectively. Results: Ethanol consumption induced hypertension and decreased the relaxation induced by AM and acetylcholine in endothelium-intact rat MAB. Phenylephrine-induced contraction was increased in endothelium-intact MAB from ethanol-treated rats. Ethanol consumption did not alter basal levels of nitrate and nitrite, nor did it affect the expression of MMP-2 or the net MMP activity in the rat MAB. Ethanol consumption increased mRNA levels of pre-pro-AM and protein levels of AM in the rat MAB. Finally, no differences in protein levels or mRNA of CRLR and RAMP1, 2 and 3 were observed after treatment with ethanol. Conclusion: Our study demonstrates that ethanol consumption increases blood pressure and the expression of AM in the vasculature and reduces the relaxation induced by this peptide in the rat MAB.

Experimental gestational hypothyroidism evokes hypertension in adult offspring rats

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n = 13) or water-treated dams (OWTD, n = 13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2 +/- 2.0 vs 108.8 +/- 3.0 mm Hg, p<0.001), SAP (157.3 +/- 2.9 vs 135.7 +/- 4.5 mm Hg, p<0.001) and DAP (109.7 +/- 1.9 vs 88.4 +/- 2.6 mm Hg, p<0.001) when compared to OWED, and had lower HR (355.1 +/- 8.9 vs 386.8 +/- 9.2 bpm, p<0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2 +/- 0.8 vs 4.0 +/- 0.6 mm Hg-2, p<0.01) in OMTD under spontaneous condition. Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old offspring, probably due to increased sympathetic modulation of vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous systems. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.

Doxycycline ameliorates 2K-1C hypertension-induced vascular dysfunction in rats by attenuating oxidative stress and improving nitric oxide bioavailability

Vascular dysfunction associated with two-kidney, one-clip (2K-1C) hypertension may result from both altered matrix metalloproteinase (MMP) activity and higher concentrations of reactive oxygen species (ROS). Doxycycline is considering the most potent MMP inhibitor of tetracyclines and attenuates 2K-1C hypertension-induced high blood pressure and chronic vascular remodeling. Doxycycline might also act as a ROS scavenger and this may contribute to the amelioration of some cardiovascular diseases associated with increased concentrations of ROS. We hypothesized that in addition to its MMP inhibitory effect, doxycycline attenuates oxidative stress and improves nitric oxide (NO) bioavailability in 2K-1C hypertension, thus improving hypertension-induced arterial endothelial dysfunction. Sham operated or 2K-1C hypertensive rats were treated with doxycycline 30 mg/kg/day (or vehicle). After 8 weeks of treatment, aortic rings were isolated to assess endothelium dependent vasorelaxation to A23187. Arterial and systemic levels of ROS were respectively measured using dihydroethidine (DHE) and thiobarbituric acid reactive substances (TBARS). Neutrophils-derived ROS were tested in vitro using the fluoroprobe Carboxy-H(2)DCFDA and human neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA). NO levels were assessed in rat aortic endothelial cells by confocal microscopy. Aortic MMP activity was determined by in situ zymography. Doxycycline attenuated 2K-1C hypertension (169 +/- 17.3 versus 209 +/- 10.9 mm Hg in hypertensive controls, p < 0.05) and protected against hypertension-induced reduction in endothelium-dependent vasorelaxation to A23187 (p < 0.05). Doxycycline also decreased hypertension-induced oxidative stress (p <= 0.05), higher MMP activity (p < 0.01) and improved NO levels in aortic endothelial cells (p < 0.01). Therefore, doxycycline ameliorates 2K-1C hypertension-induced endothelial dysfunction in aortas by inhibiting oxidative stress generation and improving NO bioavailability, in addition to its inhibitory effects on MMP activity. (C) 2012 Elsevier Inc. All rights reserved.

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 +/- 8.3 years old, FEV1: 49.3 +/- 19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.