scholarly journals Rosuvastatin Decreases Caveolin-1 and Improves Nitric Oxide–Dependent Heart Rate and Blood Pressure Variability in Apolipoprotein E −/− Mice In Vivo

Circulation ◽  
2003 ◽  
Vol 107 (19) ◽  
pp. 2480-2486 ◽  
Author(s):  
Michel Pelat ◽  
Chantal Dessy ◽  
Paul Massion ◽  
Jean-Pierre Desager ◽  
Olivier Feron ◽  
...  
2008 ◽  
Vol 79 (3) ◽  
pp. 527-536 ◽  
Author(s):  
Fanny Desjardins ◽  
Irina Lobysheva ◽  
Michel Pelat ◽  
Bernard Gallez ◽  
Olivier Feron ◽  
...  

1999 ◽  
Vol 97 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Johanna ALBERT ◽  
N. Håkan WALLÉN ◽  
Nailin LI ◽  
Claes FROSTELL ◽  
Paul HJEMDAHL

Experimental models have indicated prothrombotic effects of inhibition of nitric oxide (NO) production, and anti-thrombotic effects of inhaled NO, but the influence of NO on platelet function in vivo in humans is not well established. We therefore investigated the effects of systemic inhibition of NO synthesis by NG-monomethyl-⌊-arginine (⌊-NMMA) and of NO inhalation on platelet function in vivo. On two occasions, ⌊-NMMA (13.5 mg/kg) or saline infusion was administered to 14 healthy volunteers in a double-blind cross-over study. After a 30 min infusion of ⌊-NMMA or placebo, NO inhalation (30 p.p.m) was added during the remaining 30 min of infusion, on both occasions. Measurements included filtragometry ex vivo (reflecting platelet aggregability), flow-cytometric evaluation of platelets in whole blood (fibrinogen binding and P-selectin expression), plasma β-thromboglobulin (reflecting platelet secretion), cGMP in platelets and plasma, thrombin generation markers (thrombin fragment 1+2 and thrombin–antithrombin complexes) in plasma, and bleeding time. l-NMMA increased blood pressure and decreased heart rate. NO inhalation did not influence blood pressure or heart rate, but caused a 3-fold elevation in plasma cGMP levels (P < 0.001). Neither ⌊-NMMA nor NO influenced filtragometry readings or flow-cytometric determinations of platelet fibrinogen binding and P-selectin expression. Furthermore, plasma β-thromboglobulin, platelet cGMP and thrombin generation markers were not influenced by either treatment. Bleeding time was not influenced by ⌊-NMMA compared with placebo, but was increased by ≈ 25% during NO inhalation (P < 0.01), whether NO synthesis had been inhibited or not. The prolongation of bleeding time by inhaled NO was not accompanied by any effect on the platelet variables assessed. The present results indicate that circulating platelets are not influenced by endogenous or inhaled NO, presumably due to the rapid inactivation of NO in the blood. This does not exclude possible effects of endothelial NO in the interface between the blood and the vessel wall.


Author(s):  
Rama Lakshman ◽  
Ana-Mishel Spiroski ◽  
Lauren B. McIver ◽  
Michael P. Murphy ◽  
Dino A. Giussani

Work in preclinical animal models has established that pregnancy complicated by chronic fetal hypoxia and oxidative stress programmes cardiovascular dysfunction in adult offspring. Translating this to the human condition comes with challenges, including the early diagnosis of affected individuals to improve clinical outcomes. We hypothesize that components of programmed cardiovascular dysfunction in offspring can be identified in vivo via analysis of blood pressure variability and heart rate variability and that maternal treatment with the mitochondria-targeted antioxidant MitoQ is protective. Pregnant rats were exposed to normoxia or hypoxia (13% O 2 ) ±MitoQ (500 μM in water), from 6 to 20 days gestation. Offspring were maintained in normoxia postnatally. At 16 weeks of age, 1 male per litter was instrumented with vascular catheters and a femoral blood flow probe under isoflurane anesthesia. After recovery, arterial blood pressure and femoral flow were recorded in conscious, free-moving rats and analyzed. Offspring of hypoxic pregnancy had (1) increased very-low-frequency blood pressure variability (A) and heart rate variability (B), indices consistent with impaired endothelial function and (2) increased heart rate variability low/high-frequency ratio (C) and low-frequency blood pressure variability (D), indices of cardiac and vascular sympathetic hyperreactivity, respectively. MitoQ ameliorated A and B but not C and D. We show that asymptomatic cardiovascular dysfunction in adult offspring programmed by hypoxic pregnancy can be diagnosed in vivo by blood pressure variability and heart rate variability, suggesting that these noninvasive biomarkers could be translated to the clinical setting. MitoQ protected against programmed endothelial dysfunction but not sympathetic hyperreactivity, highlighting the divergent programming mechanisms involved.


2005 ◽  
Vol 20 (4) ◽  
pp. 394 ◽  
Author(s):  
V. Papaioannou ◽  
M. Giannakou ◽  
N. Maglaveras ◽  
E. Sofianos ◽  
M. Giala

1992 ◽  
Vol 146 (2) ◽  
pp. 155-164 ◽  
Author(s):  
A. E. HEDMAN ◽  
J. E. K. HARTIKAINEN ◽  
K. U. O. TAHVANAINEN ◽  
M. O. K. HAKUMÄKI

1982 ◽  
Vol 50 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Richard J. Roberts ◽  
Theodore C. Weerts

This study was designed to determine if visualization of anger- and fear-provoking scenes produced differential physiological patterns similar to those produced by in vivo manipulations. Normotensive college students were selected on the basis of their responses to newly developed Anger and Fear/Anxiety questionnaires and for their ability to construct arousing scenes during a screening interview. In a 2 × 2 design (intensity × emotion), four scenes (high and low anger, high and low fear) were constructed individually for each of 16 subjects to imagine. Diastolic blood pressure, systolic blood pressure, and heart rate were monitored during visualization of each scene. Change in diastolic blood pressure was significantly greater for high anger than for high fear as predicted. Analysis of change in heart rate and systolic blood pressure showed significant effects for intensity only. These results provide further support for the concept of physiological differentiation in human emotion and suggest the utility of imagery for systematic study of human emotional responding.


2004 ◽  
Vol 82 (1) ◽  
pp. 27-44 ◽  
Author(s):  
Norma Marchesini ◽  
Yusuf A Hannun

Ceramide, an emerging bioactive lipid and second messenger, is mainly generated by hydrolysis of sphingomyelin through the action of sphingomyelinases. At least two sphingomyelinases, neutral and acid sphingo myelinases, are activated in response to many extracellular stimuli. Despite extensive studies, the precise cellular function of each of these sphingomyelinases in sphingomyelin turnover and in the regulation of ceramide-mediated responses is not well understood. Therefore, it is essential to elucidate the factors and mechanisms that control the activation of acid and neutral sphingomyelinases to understand their the roles in cell regulation. This review will focus on the molecular mechanisms that regulate these enzymes in vivo and in vitro, especially the roles of oxidants (glu ta thi one, peroxide, nitric oxide), proteins (saposin, caveolin 1, caspases), and lipids (diacylglycerol, arachidonic acid, and ceramide).Key words: sphingomyelinase, ceramide, apoptosis, Niemann-Pick disease, FAN (factor associated with N-SMase activation).


2007 ◽  
Vol 44 (5) ◽  
pp. 767-778 ◽  
Author(s):  
Alessandro Beda ◽  
Frederico C. Jandre ◽  
David I.W. Phillips ◽  
Antonio Giannella-Neto ◽  
David M. Simpson

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