J de Champlain

Institut de recherches cliniques de Montréal, Montréal, Quebec, Canada

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Publications (278)1017.4 Total impact

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    ABSTRACT: The objective of the study was to evaluate the efficacy of an interdisciplinary intervention known as Educoeur in reducing cardiovascular risk and improving health behaviors in people without evidence of cardiovascular disease and to compare the Educoeur program to interventions in a specialized clinic and in usual care family practice. In a parallel, randomized, controlled trial of 185 adults with at least two modifiable cardiovascular risk factors, patients were randomly assigned to either Educoeur, specialized clinic or usual care. Cardiovascular risk, biological and lifestyle measures were assessed at baseline and at 2 years. In Educoeur, measurements were also taken before and after the lifestyle group treatment program. In 12 weeks, patients in Educoeur significantly lowered their cardiovascular risk, weight, body mass index, waist circumference, systolic blood pressure, kilocalories intake and improved their VO(2) Max and mental health. Changes remained significant at 2 years. Between group comparisons at 2 years demonstrated that Educoeur was significantly better in reducing cardiovascular risk than interventions in usual care. Together, these results highlight the importance of providing interdisciplinary programs that optimize cardiovascular risk reduction and promote active lifestyles in patients at risk of cardiovascular disease.
    Journal of Behavioral Medicine 03/2012; · 3.10 Impact Factor
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    ABSTRACT: To evaluate the capacity of chronic ASA therapy to prevent cardiac alterations and increased oxidative stress in cardiomyopathic hamsters. Male Syrian cardiomyopathic and age-matched inbred control hamsters received ASA orally from the age of 60 days. Animals were sacrificed at the age of 150, 250, and 350 days to evaluate the time course of cardiac hypertrophy and cardiovascular tissue superoxide anion (O(2)(-)) production. At the age of 150 days, the ventricular weight over body weight ratio, resting heart rate, and cardiovascular O(2)(-) production were much higher in cardiomyopathic hamsters than those in control. At the age of 250 days, in addition to the continual deterioration of these parameters with age, the blood pressure started to fall and the signs of heart failure appeared. In these cardiomyopathic hamsters, chronic ASA treatment (a) completely prevented elevated O(2)(-) production and the NAD(P)H oxidase activity, (b) significantly slowed down the development of the cardiac hypertrophy and fibrosis. Chronic ASA treatment significantly prevents the deterioration of cardiac function and structure as well as the increased oxidative stress in the cardiomyopathic hamster. Our findings suggest that ASA presents a therapeutic potential to prevent cardiac dysfunction.
    Oxidative Medicine and Cellular Longevity 01/2012; 2012:761710.
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    ABSTRACT: Inflammation and oxidative stress have been identified as integral parts in the pathogenesis of hypertension. Cyclo-oxygenase-2 which could elicit inflammation and free radicals generation appears to be a key enzyme in hypertension. Cyclo-oxygenase-2 expression and oxidative stress in cardiovascular tissues are increased in the angiotensin II model. Cyclo-oxygenase-1 and cyclo-oxygenase-2 deficient mice and their cultured aortic smooth muscle cells were used to investigate the role of these enzymes in angiotensin II induced superoxide production and hypertension. At resting state, the superoxide production in aortic and cardiac tissues was lower in cyclo-oxygenase-2 deficient than in the wild type or in cyclo-oxygenase-1 deficient mice. Chronic angiotensin II infusion increased the superoxide production in these tissues from both cyclo-oxygenase-deficient and wild-type mice whereas the level in cyclo-oxygenase-2 deficient mice was equivalent to the basal level in wild-type mice. The hypertensive effect of angiotensin II was attenuated in cyclo-oxygenase-2 deficient mice. Aspirin treatment reduced the basal superoxide production and blunted the oxidative and hypertensive effect of angiotensin II in wild type and cyclo-oxygenase-1 deficient mice whereas it lost completely its antioxidative property in angiotensin II-treated aortic smooth muscle cells isolated from cyclo-oxygenase-2 deficient mice. Cyclo-oxygenase-2 pathway plays a major role in the superoxide generation as well as in the angiotensin II-induced oxidative stress and blood pressure. Cyclo-oxygenase-1 activity didn't show any influence on these parameters. These results suggest that cyclo-oxygenase-2 is involved in the pathogenesis of hypertension.
    American Journal of Hypertension 08/2011; 24(11):1239-44. · 3.67 Impact Factor
  • Journal of Electrocardiology 03/2011; 44(2). · 1.09 Impact Factor
  • Sylvain Foucart, Jacques de Champlain, Réginald Nadeau
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    ABSTRACT: The combined effect of a β2-antagonist and an α2-agonist on the release of adrenal catecholamines was studied in the anaesthetized and vagotomized dog. The electrical stimulation of the splanchnic nerve (5-V pulses of 2 ms duration for 3 min at a frequency of 3 Hz) produced a significant rise in adrenal catecholamine release in the adrenal vein. Intravenous injection of a β2-antagonist significantly reduced this response and a subsequent injection of an α2-agonist further reduced the release of catecholamines. However, if the α2-agonist is injected first, the release is not different compared with the control stimulation, and the subsequent injection of the β2-antagonist also did not modify the release in response to electrical stimulation. These results suggest that the blockade of presynaptic β2-receptors reduces the release of adrenal catecholamines without interfering with the activation of the α2-adrenoceptors. In contrast, the pretreatment with the α2-agonist, which does not modify the release of catecholamine at 3 Hz, seems to interfere with the inhibitory effect of the β2-antagonist.
    Canadian Journal of Physiology and Pharmacology 02/2011; 66(10):1340-1343. · 1.56 Impact Factor
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    ABSTRACT: It has been reported that HMG-CoA reductase inhibitors such as atorvastatin induce vascular smooth muscle cell (SMC) apoptosis in vitro. However, this effect remains to be demonstrated in vivo. The present studies were designed to test the ability of atorvastatin to induce SMC apoptosis in vivo, using the spontaneously hypertensive rat (SHR) as a well-known reference model of SMC apoptosis induction in vivo by cardiovascular drugs including the calcium channel blocker amlodipine. Atorvastatin was administered to SHR for 3 or 6 weeks either alone or together with amlodipine, a drug combination clinically available to patients. Primary endpoints included aortic medial hypertrophy and aortic SMC hyperplasia, internucleosomal DNA fragmentation and expression of the apoptosis regulatory proteins Bax and Bcl-2. The SHR aorta showed no evidence of SMC apoptosis induction by atorvastatin, even at the high dose of 50 mg kg(-1) day(-1), although the statin significantly reduced oxidative stress after 3 weeks and blood pressure after 6 weeks of administration. Amlodipine-induced regression of aortic hypertophy and aortic SMC hyperplasia were dose- and time-dependent, but there was no interaction between atorvastatin and amlodipine in modulating the primary endpoints. These results do not support the notion that atorvastatin induces SMC apoptosis in the aortic media in vivo.
    Vascular Pharmacology 10/2010; 54(1-2):5-12. · 3.21 Impact Factor
  • R Wu, J de Champlain, H Girouard
    Journal of Hypertension - J HYPERTENSION. 01/2010; 28.
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    ABSTRACT: To determine the contribution of nitric oxide (NO) in cardiovascular remodeling associated to hypertension and insulin resistance, male Sprague-Dawley rats received tap water supplemented or not (control), with 10% D-glucose (G) and/or 50 mg x kg(-1) x d(-1) L-NAME to inhibit NO synthase (G-LN or LN) for 4 weeks. Systolic blood pressure increased by 12%, 26%, and 39% with G, LN, and G-LN treatments, respectively. Hyperinsulinemia and insulin resistance (homeostasis model assessment index) occurred in G-treated rats (P < 0.05) and were further increased in G-LN (P < 0.01). Plasma adrenaline concentrations were markedly increased in all treated groups, especially in G-LN (P < 0.01), whereas noradrenaline was increased in G-treated rats only. Whereas no cardiac hypertrophy or fibrosis was detected, aortic hypertrophy occurred in LN and G-LN rats (P < 0.001) without smooth muscle hyperplasia. Superoxide anion formation was increased in the aorta of all treated groups (P < 0.01) and in the heart of LN (P < 0.05), but reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity was not affected. In conclusion, the loss of the wide-range protective effects of NO, the increased vascular oxidative stress, and the sympathoadrenal hyperactivity are among the contributing factors leading to the exacerbation of hypertension and insulin resistance in G-LN. These factors were sufficient to cause vascular but not cardiac hypertrophy.
    Journal of cardiovascular pharmacology 04/2009; 53(5):405-13. · 2.83 Impact Factor
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    ABSTRACT: Objective To study the role of the serotoninergic 5-HT2B receptor in the development of cardiac hypertrophy and its link with left ventricular superoxide anion generation in a mouse model of angiotensin II-induced hypertension. Methods Wild-type and 5-HT2B receptor knock-out (KO) mice were perfused with angiotensin II (0.2 mg.kg-1.d-1) for 14 days with or without SB215505 (1 mg.kg-1.d-1), an antagonist of the 5-HT2B receptor. Heart rate and blood pressure were measured by tail-cuff plethysmography. Cardiac hypertrophy was evaluated by echocardiography and direct measurement of heart weight. Superoxide anion production and maximal NAD(P)H oxidase activity were measured by a chemiluminescence method using lucigenin. Superoxide anion production was also measured in primary left ventricular fibroblasts cell cultures. Results Angiotensin II increased superoxide anion production (+32 %), the maximal activity of NAD(P)H oxidase (+84 %) in left ventricle of wild-type mice concomitantly with the arterial blood pressure (+37mmHg) and the heart/body weight ratio (+17 %). A pharmacological blockade (SB215505) or a genetic suppression of the 5-HT2B receptor prevented the increased superoxide anion production and cardiac hypertrophy but had no effect on cardiac hemodynamics or blood pressure. Angiotensin II also increased NAD(P)H oxidase activity in cultured cardiac fibroblasts and this increase was prevented by SB215505. Conclusion The 5-HT2B receptor is a new potential target for the prevention of cardiac hypertrophy and its associated superoxide anion production. Cells of the extracellular matrix could possibly be involved in this mechanism.
    Archives of Cardiovascular Diseases - ARCH CARDIOVASC DIS. 01/2009; 102.
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    ABSTRACT: Beneficial effects of an antioxidant (N-acetyl-L-cysteine, NAC) and an angiotensin I-converting enzyme (ACE) inhibitor (ramipril) were assessed in a rat model of insulin resistance induced by 10% glucose feeding for 20 weeks. Treatments with NAC (2 g/kg per day) and ramipril (1 mg/kg per day) were initiated at 16 weeks in the drinking fluid. Systolic blood pressure, plasma levels of insulin and glucose, and insulin resistance were significantly higher in rats treated with glucose for 20 weeks. This was associated with a higher production of superoxide anion and NADPH oxidase activity in aorta and liver and with a marked reduction in protein expression of skeletal muscle insulin receptor substrate-1 (IRS-1) in the gastrocnemius muscle. NAC prevented all these alterations. Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta. Ramipril, in contrast to NAC, did not reduce NADPH oxidase activity in aorta and liver or plasma levels of 4-hydroxynonenal and malondialdehyde. Results suggest that the inhibition of the oxidative stress in hypertensive and insulin-resistant states contributes to the therapeutic effects of NAC and ramipril. Whereas NAC exerts effective antioxidant activity in multiple tissues, ramipril appears to preferentially target the vasculature.
    Canadian Journal of Physiology and Pharmacology 11/2008; 86(11):752-60. · 1.56 Impact Factor
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    ABSTRACT: Midodrine is an alpha-agonist prodrug of desglymidodrine (DGM) that has been reported to be of clinical benefit in patients with neurocardiogenic syncope. Its effects may be mediated not only by its hypertensive properties but also by its neurohumoral influences independent of blood pressure (BP). The present study aimed to simultaneously characterize the effects of midodrine on BP, plasma catecholamines, plasma atrial natriuretic peptide (ANP), and power spectral analysis of heart rate (HR) in healthy volunteers. This was a prospective, randomized, single-blind, 2-period, crossover study in which a single, oral, 5-mg dose of midodrine was compared with placebo. The washout period between midodrine and placebo was 1 week. The study parameters included plasma DGM (as measured by high-performance liquid chromatography [HPLC]); systolic and diastolic BP (as measured with an oscillometric monitor); HR; plasma catecholamines (measured by HPLC); plasma ANP, also known as venous return (measured by a radio-immunoassay); and low- and high-frequency HR variation (calculated from computerized 5-minute electrocardiographic recordings). All study parameters were measured simultaneously 12 times just before and over a period of 8 hours after drug administration. Fifteen healthy nonsmoking male subjects (14 white, 1 black; mean [SD] age, 28.6 [4.7] years; weight, 74.5 [16.4] kg; seated BP, 109.9 [9.0]/73.6 [9.5] mm Hg; seated HR, 63.8 [8.4] bpm) were randomized. No significant effects of midodrine on BP were observed. At Cmax, midodrine decreased norepinephrine from 188.4 (30.6) to 162.5 (29.8) pg/mL (P = 0.011) and HR from 57.2 (7.3) to 54.9 (6.6) bpm (P = 0.022). A significant correlation was found between DGM concentration and HR ( varphi -0.61; P = 0.014). A DGM-related increase in plasma ANP (+29.6 [90.0] fmoL/mL) was observed. This study in healthy male volunteers found that midodrine has sympatholytic influences that are independent of BP but related to augmented venous return.
    Clinical Therapeutics 10/2008; 30(9):1629-38. · 2.23 Impact Factor
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    ABSTRACT: We established previously that 5-HT(2B) receptors are involved in cardiac hypertrophy through the regulation of hypertrophic cytokines in cardiac fibroblasts. Moreover, the generation of reactive oxygen species and tumor necrosis factor-alpha through the activation of reduced nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase has been implicated in cardiac hypertrophy. In this study, we investigated whether 5-HT(2B) receptors could be involved in the development of cardiac hypertrophy associated with superoxide anion production. Therefore, we measured the effects of serotonergic 5-HT(2B) receptor blockade on left-ventricular superoxide anion generation in 2 established pharmacological models of cardiac hypertrophy, ie, angiotensin II and isoproterenol infusions in mice. Angiotensin II infusion for 14 days increased superoxide anion concentration (+32%), NAD(P)H oxidase maximal activity (+84%), and p47(phox) NAD(P)H oxidase subunit expression in the left ventricle together with hypertension (+37 mm Hg) and cardiac hypertrophy (+17% for heart weight:body weight). The 5-HT(2B) receptor blockade by a selective antagonist (SB215505) prevented the increase in cardiac superoxide generation and hypertrophy. Similarly, infusion for 5 days of isoproterenol increased left-ventricular NAD(P)H oxidase activity (+48%) and cardiac hypertrophy (+31%) that were prevented by the 5-HT(2B) receptor blockade. Finally, in the primary culture of left-ventricular cardiac fibroblasts, angiotensin II and isoproterenol stimulated NAD(P)H oxidase activity. This activation was prevented by SB215505. These findings suggest that the 5-HT(2B) receptor may represent a new target to reduce cardiac hypertrophy and oxidative stress. Its blockade affects both angiotensin II and beta-adrenergic trophic responses without significant hemodynamic alteration.
    Hypertension 07/2008; 52(2):301-7. · 6.87 Impact Factor
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    ABSTRACT: The effect of age on autonomic nervous system was assessed at rest and while standing using systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, and power spectral analysis of the time duration between 2 consecutive R waves of an electrocardiogram (RR) interval variability, as well as on plasma norepinephrine and epinephrine levels in mild to moderate hypertensive patients (DBP, 90-110 mm Hg). Patients younger than 60 years (n=57) and older than 60 years (n=32), were evaluated after a 3- to 4-week placebo period. Plasma catecholamines were measured in the supine position at rest and after 10 minutes of standing. Power spectral analysis of the RR interval variability was performed in each condition using the high-frequency (HF) band (0.15-0.4 Hz) as an index of parasympathetic activity and the low-frequency (LF) band (0.05-0.15 Hz) and LF-HF ratio to estimate sympathetic activity. The total power was calculated as the sum of LF and HF power. supine SBP was significantly higher in older patients (P<.05). SBP and DBP increased significantly only in younger patients during standing (P<.05), while the changes were smaller and nonsignificantly lower in older patients. HR was similar in both groups at rest and increased similarly during standing. Norepinephrine and epinephrine levels were similar at rest and increased similarly in both groups of patients during standing. At rest, lower LF and HF components were observed in older patients. The LF component increased less and the HF component decreased less in older patients during standing. A lower sympathetic and parasympathetic basal cardiac tone was observed at rest in older hypertensive patients. Moreover, reduced hemodynamic and sympathetic responses to standing as assessed by SBP, DBP, and the LF component of HR variability were observed in older hypertensives in the presence of a normal catecholamine response. These observations could reflect a decreased sensitivity of cardiac beta-adrenoceptors with aging.
    Journal of Clinical Hypertension 02/2008; 10(2):97-104. · 2.36 Impact Factor
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    ABSTRACT: Diabetes causes sensory polyneuropathy with associated pain in the form of tactile allodynia and thermal hyperalgesia which are often intractable and resistant to current therapy. This study tested the beneficial effects of the non-peptide and orally active kinin B(1) receptor antagonist SSR240612 against tactile and cold allodynia in a rat model of insulin resistance. Rats were fed with 10% D-glucose for 12 weeks and effects of orally administered SSR240612 (0.3-30 mg kg(-1)) were determined on the development of tactile and cold allodynia. Possible interference of SSR240612 with vascular oxidative stress and pancreatic function was also addressed. Glucose-fed rats exhibited tactile and cold allodynia, increases in systolic blood pressure and higher plasma levels of insulin and glucose, at 12 weeks. SSR240612 blocked tactile and cold allodynia at 3 h (ID(50)=5.5 and 7.1 mg kg(-1), respectively) in glucose-fed rats but had no effect in control rats. The antagonist (10 mg kg(-1)) had no effect on plasma glucose and insulin, insulin resistance (HOMA index) and aortic superoxide anion production in glucose-fed rats. We provide the first evidence that the B(1) receptors are involved in allodynia in an experimental rat model of insulin resistance. Allodynia was alleviated by SSR240612 most likely through a direct inhibition of B(1) receptors affecting spinal cord and/or sensory nerve excitation. Thus, orally active non-peptide B(1) receptor antagonists should have clinical therapeutic potential in the treatment of sensory polyneuropathy.
    British Journal of Pharmacology 10/2007; 152(2):280-7. · 5.07 Impact Factor
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    ABSTRACT: Isolated systolic hypertension results from a gradual stiffening of large arteries, to which medial elastocalcinosis (calcification of elastic lamellae) contributes. There is compelling evidence that reactive oxygen species (ROS) are associated with several disease processes affecting the cardiovascular system, including hypertension. The present study was designed to investigate whether the inhibition of ROS production by alpha-lipoic acid can prevent vascular calcification. Sprague-Dawley rats were treated with warfarin (20 mg/kg/day) and vitamin K (15 mg/kg/day) (WVK) for 4 weeks to induce large artery calcification. Subgroups received either a normal diet or a diet supplemented with lipoic acid (1000 mg/kg/day). The WVK treatment produced a small elevation of aortic superoxide levels that did not reach statistical significance. Alpha-lipoic acid reduced the elevation below baseline levels. In rats treated with alpha-lipoic acid, the WVK-induced elevation of pulse wave velocity (an index of arterial stiffness), left ventricular hypertrophy, and aortic, femoral and carotid elastocalcinosis were not prevented. Although a contribution of oxidative stress has been suggested in the aging cardiovascular system, this alteration does not appear to contribute to the calcification process and the subsequent stiffening of large arteries in the animal model tested.
    Vascular Pharmacology 04/2007; 46(3):201-6. · 3.21 Impact Factor
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    ABSTRACT: To compare the effects of valsartan and amlodipine alone or in combination on plasma norepinephrine (NE) at rest and standing for 10 minutes in patients with hypertension, 47 patients with a sitting diastolic blood pressure (BP) (DBP)>95 mm Hg and<110 mm Hg were randomized in a double-blind fashion to either valsartan or amlodipine. During the first 4 weeks of treatment, patients received a low dose of either valsartan (80 mg) or amlodipine (5 mg). The patients were force-titrated to the high dose of either drug (160 or 10 mg) for 4 weeks. After 8 weeks of therapy, those who still had a DBP>90 mm Hg (nonresponders) received combination therapy with the other drug, whereas patients with a DBP<90 mm Hg (responders) continued on monotherapy. Decreases in ambulatory BP and clinic systolic BP and DBP were significant (P<.05) after 8 weeks' therapy with no difference between the 2 groups. Amlodipine but not valsartan as monotherapy consistently increased NE levels at rest and enhanced NE levels during standing. Valsartan decreased basal NE in responders. Combination therapy with valsartan and amlodipine did not attenuate the rise in NE levels induced by amlodipine. This study indicates that therapy with amlodipine increases peripheral sympathetic basal tone and reactivity to standing in patients with hypertension, whereas valsartan does not. Combined therapy with amlodipine/valsartan did not attenuate the sympathetic activation induced by amlodipine. The hypotensive action of valsartan may be mediated in part by an inhibition of the sympathetic baroreflex in patients with hypertension.
    Journal of Clinical Hypertension 03/2007; 9(3):168-78. · 2.36 Impact Factor
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    ABSTRACT: Endothelin (ET) modulates cellular processes relevant to vascular remodeling, but there is still some debate as to the potential of ET to be a trophic factor or a mitogen. Moreover, the signaling of ET in vivo to produce these effects is largely unknown. 3H-leucine and 3H-thymidine incorporation in rat small mesenteric arteries was studied with several doses of ET-1 (0.1-10 pmol/kg/min) administered for 26 h in vivo. The EC50 for protein synthesis was four times lower than that of DNA synthesis, with maximal effects around 1 and 3 pmol/kg/min, respectively. At 5 pmol/kg/min, ET enhanced CDK2 activity by reducing the binding of its inhibitor p27(Kip1). In contrast, the binding was enhanced at 0.5 pmol/kg/min. The reduced binding observed at 5 pmol/kg/min could not be explained by changes of p27(Kip1) or CDK2 content. Phosphorylation of p27(Kip1) on serine 10 was significantly reduced at 5 pmol/kg/min ET. Although the phosphoinositide 3-kinase pathway was activated, it did not contribute to the protein or DNA synthesis responses. Administration of 1 or 5 pmol/kg/min ET-1 for 28 days increased the thickness and cross-sectional area of the small mesenteric artery due to hypertrophy and hyperplasia, respectively, thus confirming the results obtained in acute conditions. ET modulates p27(Kip1) binding to CDK2, producing hypertrophy at low and hyperplasia at higher concentrations. Taken together, these results suggest that ET can act both as a trophic factor and as a mitogen in an in vivo environment, depending on its local concentration.
    Cardiovascular Research 08/2006; 71(1):61-8. · 5.81 Impact Factor
  • Adil El Midaoui, Lingyun Wu, Rui Wang, Jacques de Champlain
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    ABSTRACT: The aim of the present study was to examine the chronic effects of alpha-lipoic acid on proliferator peroxisome activated receptors-gamma (PPAR-gamma) and PPAR-alpha expressions in cardiovascular tissues of chronically hypertensive insulinoresistant rats. We have also evaluated the chronic effects of high levels of insulin, glucose, or both on superoxide anion (O(2)(-)) production in aortic smooth muscle cells (SMCs) in the presence or in absence of pioglitazone, a PPAR-gamma agonist. The PPAR-gamma and PPAR-alpha expressions were measured by Western blot. The oxidative stress was evaluated by measuring the O(2)(-) production using the lucigenin method. Increases in blood pressure, in aortic O(2)(-) production, in glucose or insulin levels, and in insulin resistance, as well as the decrease in PPAR-gamma protein levels in aorta and heart tissues were prevented or attenuated in glucose-treated rats fed with lipoic acid. Chronic treatment with pioglitazone prevented the marked increase in O(2)(-) production in cultured SMCs chronically treated with high insulin combined or not with high glucose levels. The combined therapy with the antioxidant alpha-lipoic acid restored PPAR-gamma levels in cardiovascular tissues and attenuated or prevented the development of insulin resistance and hypertension in chronically glucose-fed rats. Moreover, the finding that pioglitazone was also efficient in preventing the increase in oxidative stress in SMCs treated with high insulin combined with high glucose concentrations supports the hypothesis that the activation of PPAR-gamma activity can counteract the oxidative stress that seems to be implicated in the development of hypertension and insulin resistance.
    American Journal of Hypertension 05/2006; 19(4):407-12. · 3.67 Impact Factor
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    ABSTRACT: To examine whether 2 sympatholytic medications decrease sleep bruxism and prevent the rise in sympathetic activity preceding the onset of sleep bruxism: propranolol, a nonselective adrenergic beta-blocker, and clonidine, a selective alpha2-agonist. Experimental randomized controlled crossover studies with placebo and active treatments (propranolol 120 mg; clonidine 0.3 mg). Hospital-based sleep research laboratory. Twenty-five subjects with a history and diagnosis of SLEEP BRUXISM (11 men, 14 women; age range, 21 to 31 years). Polygraphic study. Polygraphic sleep laboratory recordings were done for 4 nights: the first night was habituation, the second, sleep bruxism diagnosis; and 3 and 4 were study nights. The sleep bruxism index was estimated using masseter muscle activity. Heart rate variability was estimated with spectral analysis of RR intervals. Sleep and sleep bruxism variables were not significantly influenced by propranolol. A reduction of the mean RR intervals and of the sympathetic dominance (p < .05) was seen. Under clonidine, duration of sleep stage 2 was prolonged, whereas REM sleep was suppressed in 14 of 16 subjects with sleep bruxism. The sleep bruxism index was reduced by 61% (p < .05). Under clonidine, a reduction in heart rate and sympathetic dominance was observed in stable sleep and in the minute preceding the onset of sleep bruxism (p < .05). Although propranolol did not affect sleep bruxism, clonidine decreased sympathetic tone in the minute preceding the onset of sleep bruxism, thus reducing sleep bruxism by preventing the sequence of autonomic to motor activation of sleep bruxism. This further supports the role of sympathetic activity in the pathophysiology of sleep bruxism. Because morning hypotension was seen in 19% of patients, further dose-dependant research is required to assess the safety of clonidine for the management of sleep bruxism.
    Sleep 03/2006; 29(3):307-16. · 5.10 Impact Factor
  • Marc-André Laplante, Jacques de Champlain
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    ABSTRACT: The NAD(P)H oxidase is an enzyme assembled at the cellular membrane able to produce superoxide anion from NADH or NAD(P)H (nicotinamide adenine dinucleotide phosphate). It is one of the main sources of superoxide anion in cardiovascular tissues and its role in a variety of cardiovascular disorders such as atherosclerosis, cardiac hypertrophy, and endothelial dysfunction was recently proposed. Although, many factors and receptors were shown to lead to the activation of the enzyme, particulary the type 1 angiotensin receptor, the pathways involved are still widely unknown. Despite the identification of factors such as c-Src and protein kinase C implicated in the acute activation of NAD(P)H oxidase, the signalling involved in the sustained activation of the enzyme is probably far more complex than was previously envisioned. In this review, we describe the role of endothelin-1 in NAD(P)H oxidase signalling after a sustained stimulation by angiotensin II. Since most pathologies caused by an NAD(P)H oxidase overactivation develop over a relatively long period of time, it is necessary to better understand the long-term signalling of the enzyme for the development or use of more specific therapeutic tools.
    Canadian Journal of Physiology and Pharmacology 02/2006; 84(1):21-8. · 1.56 Impact Factor

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4k Citations
1,017.40 Total Impact Points


  • 2004–2012
    • Institut de recherches cliniques de Montréal
      Montréal, Quebec, Canada
  • 1974–2009
    • Université de Montréal
      • • Faculty of Medicine
      • • Department of Physiology
      • • Faculty of Pharmacy
      • • Department of Radiology, Radiation Oncology and Nuclear Medicine
      Montréal, Quebec, Canada
  • 2008
    • University of Toronto
      Toronto, Ontario, Canada
  • 1983–2006
    • Université du Québec à Montréal
      • • Department of Sociology
      • • Department of Kinanthropology
      Montréal, Quebec, Canada
  • 1983–2005
    • Montreal Heart Institute
      • Department of Medicine
      Montréal, Quebec, Canada
  • 1994–2004
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 1989–1998
    • Hôpital du Sacré-Coeur de Montréal
      Montréal, Quebec, Canada
  • 1997
    • University of Grenoble
      Grenoble, Rhône-Alpes, France
  • 1991–1993
    • Université de Sherbrooke
      • • Division of Cardiology
      • • Department of Physiology and Biophysics
      Sherbrooke, Quebec, Canada
  • 1969
    • National Institute of Mental Health (NIMH)
      • Laboratory of Clinical Science
      Maryland, United States
  • 1963
    • Hotel Dieu Hospital
      Kingston, Ontario, Canada