The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Guillaume Mahé - One of the best experts on this subject based on the ideXlab platform.
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Neurovascular microcirculatory Vasodilation mediated by C-fibers and Transient receptor potential vanilloid-type-1 channels (TRPV 1) is impaired in type 1 diabetes
Scientific Reports, 2017Co-Authors: Pauline Marche, Séverine Dubois, Pierre Abraham, Elsa Parot-schinkel, Lydie Gascoin, Anne Humeau-heurtier, Pierre-henry Ducluzeau-fieloux, Guillaume MahéAbstract:Microvascular dysfunction may have an early onset in type 1 diabetes (T1D) and can precede major complications. Our objectives were to assess the endothelial-dependent (acetylcholine, ACh; and post-occlusive hyperemia, PORH), non-endothelial-dependent (sodium nitroprusside, SNP) and neurovascular-dependent (local heating, LH and current induced Vasodilation, CIV) microcirculatory Vasodilation in T1D patients compared with matched control subjects using a laser speckle contrast imager. Seventeen T1D patients - matched with 17 subjects according to age, gender, Body-Mass-Index, and smoking status - underwent macro- and microvascular investigations. The LH early peak assessed the transient receptor potential vanilloid type 1 channels (TRPV1) mediated Vasodilation, whereas the plateau assessed the Nitirc-Oxyde (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways. PORH explored sensory nerves and (EDHF), while CIV assessed sensory nerves (C-fibers) and prostaglandin-mediated Vasodilation. Using neurological investigations, we observed that C-fiber and A-delta fiber functions in T1D patients were similar to control subjects. PORH, CIV, LH peak and plateau Vasodilations were significantly decreased in T1D patients compared to controls, whereas there was no difference between the two groups for ACh and SNP Vasodilations. Neurovascular microcirculatory Vasodilations (C-fibers and TRPV 1-mediated Vasodilations) are impaired in TD1 patients whereas no abnormalities were found using clinical neurological investigations. Clinicaltrials: No. NCT02538120.
Duxin Qing - One of the best experts on this subject based on the ideXlab platform.
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tanshinone iia elicited Vasodilation in rat coronary arteriole roles of nitric oxide and potassium channels
European Journal of Pharmacology, 2009Co-Authors: Guobao Wu, Enxiang Zhou, Duxin QingAbstract:Abstract Salvia miltiorrhiza has been widely used in the treatment of various cardiovascular diseases due to its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone IIA, the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was shown to induce Vasodilation in coronary arteries. But its effects on coronary arterioles remain unknown. The purpose of this study was to investigate the effects of tanshinone IIA on isolated rat coronary arteriole and the underlying mechanisms. Coronary arterioles were carefully dissected, cannulated and pressurized. Tanshinone IIA-elicited vascular inner diameter change was recorded by a computerized diameter tracking system. To investigate the mechanisms governing the vasodilative effects of tanshinone IIA, the roles of endothelium, endothelium-derived vasoactive factors and potassium channels were assessed respectively. Endothelium denudation, inhibition of nitric oxide synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of the large conductance calcium(Ca2+)-activated potassium channels (BKca) significantly decreased the Vasodilation elicited by Tanshinone IIA. The results indicated that tanshinone IIA induces an endothelium-dependent Vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450 metabolites contribute to the Vasodilation; activation of BKca channels plays an important role in the Vasodilation.
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tanshinone iia elicited Vasodilation in rat coronary arteriole roles of nitric oxide and potassium channels
European Journal of Pharmacology, 2009Co-Authors: Guobao Wu, Enxiang Zhou, Duxin QingAbstract:Abstract Salvia miltiorrhiza has been widely used in the treatment of various cardiovascular diseases due to its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone IIA, the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was shown to induce Vasodilation in coronary arteries. But its effects on coronary arterioles remain unknown. The purpose of this study was to investigate the effects of tanshinone IIA on isolated rat coronary arteriole and the underlying mechanisms. Coronary arterioles were carefully dissected, cannulated and pressurized. Tanshinone IIA-elicited vascular inner diameter change was recorded by a computerized diameter tracking system. To investigate the mechanisms governing the vasodilative effects of tanshinone IIA, the roles of endothelium, endothelium-derived vasoactive factors and potassium channels were assessed respectively. Endothelium denudation, inhibition of nitric oxide synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of the large conductance calcium(Ca2+)-activated potassium channels (BKca) significantly decreased the Vasodilation elicited by Tanshinone IIA. The results indicated that tanshinone IIA induces an endothelium-dependent Vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450 metabolites contribute to the Vasodilation; activation of BKca channels plays an important role in the Vasodilation.
Mark A Creager - One of the best experts on this subject based on the ideXlab platform.
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estradiol therapy combined with progesterone and endothelium dependent Vasodilation in postmenopausal women
Circulation, 1998Co-Authors: Marie D Gerhard, Shelly J Creager, Ahmed Tawakol, Peter Ganz, Brian W Walsh, Elizabeth A Haley, Ellen W Seely, Mark A CreagerAbstract:Background—Epidemiological studies indicate that estrogen replacement therapy decreases the risk of cardiovascular events in postmenopausal women. Estrogen may confer cardiovascular protection by improving endothelial function because it increases endothelium-dependent Vasodilation. It is not known whether progesterone attenuates the beneficial effects of estrogen on endothelial function. Methods and Results—Seventeen postmenopausal women with mild hypercholesterolemia were enrolled in a placebo-controlled, crossover trial to evaluate the effect of transdermal estradiol, with and without vaginal micronized progesterone, on endothelium-dependent Vasodilation in a peripheral conduit artery. Brachial artery diameter was measured with high-resolution B-mode ultrasonography. To assess endothelium-dependent Vasodilation, brachial artery diameter was determined at baseline and after a flow stimulus induced by reactive hyperemia. To assess endothelium-independent Vasodilation, brachial artery diameter was measure...
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hyperhomocyst e inemia is associated with impaired endothelium dependent Vasodilation in humans
Circulation, 1997Co-Authors: Ahmed Tawakol, Marie D Gerhard, Torbjorn Omland, Mark A CreagerAbstract:Background Hyperhomocyst(e)inemia is a risk factor for atherosclerosis and is prevalent in the elderly. The objective of this study was to determine whether hyperhomocyst(e)inemia is associated with impaired endothelium-dependent Vasodilation in humans. Methods and Results High-resolution vascular ultrasonography was used to study endothelium-dependent and -independent Vasodilation in a nonatherosclerotic peripheral conduit artery of 26 elderly hyperhomocyst(e)inemic subjects and 15 age- and sex-matched subjects with normal homocysteine levels. Flow-mediated, endothelium-dependent (nitric oxide–mediated) Vasodilation was assessed by measuring the percent change in brachial artery diameter during reactive hyperemia. Endothelium-independent Vasodilation was assessed after the administration of 0.4 mg sublingual nitroglycerin. Endothelium-dependent Vasodilation was significantly impaired in the hyperhomocyst(e)inemic subjects compared with control subjects (3.7±0.6% versus 8.1±1.2%; P =.004), whereas endothelium-independent Vasodilation was not different between the two groups (10.1±1.6% versus 9.3±1.5%; P =NS). In a linear regression analysis with serum homocysteine concentration, folic acid, age, sex, cholesterol (serum total, LDL, or HDL cholesterol), mean arterial blood pressure, use of antihypertensive medication, and baseline brachial artery diameter included as covariates, serum homocysteine concentration emerged as the only significant predictor of flow-mediated Vasodilation. Conclusions These data indicate that hyperhomocyst(e)inemia is associated with impaired endothelium-dependent Vasodilation in humans and suggest that the bioavailability of nitric oxide is decreased in hyperhomocyst(e)inemic humans. ( . 1997;95:1119-1121.)
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flow induced Vasodilation of the human brachial artery is impaired in patients 40 years of age with coronary artery disease
American Journal of Cardiology, 1996Co-Authors: Eric H Lieberman, Marie D Gerhard, Akimi Uehata, Andrew P Selwyn, Peter Ganz, Alan C Yeung, Mark A CreagerAbstract:The objective of this study was to determine whether abnormal flow-induced endothelium-dependent Vasodilation in the brachial artery identifies young patients with coronary artery disease (CAD). High-resolution ultrasonography was used to measure vascular reactivity in a peripheral conduit vessel, the brachial artery, in 14 young men with CAD and in 11 age-matched, healthy, male volunteers. Endothelium-dependent Vasodilation was determined by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia. Endothelium-independent Vasodilation was assessed by administration of sublingual nitroglycerin. To ascertain whether flow-mediated Vasodilation in humans is mediated by endothelium-derived nitric oxide, brachial artery diameter was measured during reactive hyperemia, before and during administration of the nitric oxide synthase antagonist NG-monomemyl-l-arginine (l-NMMA). Brachial artery diameter was also measured during intraarterial infusion of acetylcholine and nitroprusside before and after administration of l-NMMA. Flow-induced Vasodilation was less in patients with CAD than in healthy volunteers (1.3 ± 1.1% vs 6.2 ± 0.7%, p < 0.05). Nitroglycerin increased brachial artery diameter similarly in each subject group (11.3 ± 1.0% vs 15.8 ± 1.2%, p = NS). l-NMMA inhibited flow-mediated Vasodilation and the vasodilative response to acetylcholine, but did not affect the response to nitroprusside. It is concluded that abnormal flow-induced endothelium-dependent Vasodilation occurs in the brachial artery of young patients with CAD.
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aging progressively impairs endothelium dependent Vasodilation in forearm resistance vessels of humans
Hypertension, 1996Co-Authors: Marie D Gerhard, Maryanne Roddy, Shelly J Creager, Mark A CreagerAbstract:Studies in experimental models suggest that endothelium-derived nitric oxide is reduced with aging, and this circumstance may be relevant to atherogenesis. The aim of this study was to determine whether increasing age resulted in altered endothelium-dependent Vasodilation in the forearm resistance vessels of healthy humans. Forearm blood flow was measured in 119 healthy subjects, aged 19 to 69 years, by venous occlusion plethysmography. Brachial artery infusions of methacholine chloride (0.03 to 10.0 microgram/min) were used to assess endothelium-dependent Vasodilation and of sodium nitroprusside (0.03 to 10.0 microgram/min) to assess endothelium-independent Vasodilation. The slope of the dose-blood flow response relation was calculated in each subject for each drug. Univariate and multiple stepwise regression analyses were used to relate vascular reactivity to selected variables, including age, lipids, and blood pressure. Endothelium-dependent Vasodilation was progressively impaired with increasing age, assessed as a reduction in slope from 2.25 +/- 0.16 to 0.34 +/- 0.11 (mL/100 mL tissue per minute)/(microgram/min) (P <.001). The decline in endothelium-dependent Vasodilation was already evident by the fourth decade (age 30 to 39 years). Endothelium-independent Vasodilation did not change with age. Age, total cholesterol, and low-density lipoprotein cholesterol were univariate predictors of endothelium-dependent Vasodilation. Age remained the most significant predictor of endothelium-dependent vasodilator responses by multiple stepwise regression analysis. From these observations, it can be concluded that endothelium-dependent Vasodilation declines steadily with increasing age in healthy human subjects. Age is a strong univariate and multivariate predictor of endothelium-dependent Vasodilation. This finding may be a marker for more widespread endothelial dysfunction.
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aging progressively impairs endothelium dependent Vasodilation in forearm resistance vessels of humans
Hypertension, 1996Co-Authors: Marie D Gerhard, Maryanne Roddy, Shelly J Creager, Mark A CreagerAbstract:Abstract Studies in experimental models suggest that endothelium-derived nitric oxide is reduced with aging, and this circumstance may be relevant to atherogenesis. The aim of this study was to determine whether increasing age resulted in altered endothelium-dependent Vasodilation in the forearm resistance vessels of healthy humans. Forearm blood flow was measured in 119 healthy subjects, aged 19 to 69 years, by venous occlusion plethysmography. Brachial artery infusions of methacholine chloride (0.03 to 10.0 μg/min) were used to assess endothelium-dependent Vasodilation and of sodium nitroprusside (0.03 to 10.0 μg/min) to assess endothelium-independent Vasodilation. The slope of the dose–blood flow response relation was calculated in each subject for each drug. Univariate and multiple stepwise regression analyses were used to relate vascular reactivity to selected variables, including age, lipids, and blood pressure. Endothelium-dependent Vasodilation was progressively impaired with increasing age, assessed as a reduction in slope from 2.25±0.16 to 0.34±0.11 (mL/100 mL tissue per minute)/(μg/min) ( P
Pauline Marche - One of the best experts on this subject based on the ideXlab platform.
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Neurovascular microcirculatory Vasodilation mediated by C-fibers and Transient receptor potential vanilloid-type-1 channels (TRPV 1) is impaired in type 1 diabetes
Scientific Reports, 2017Co-Authors: Pauline Marche, Séverine Dubois, Pierre Abraham, Elsa Parot-schinkel, Lydie Gascoin, Anne Humeau-heurtier, Pierre-henry Ducluzeau-fieloux, Guillaume MahéAbstract:Microvascular dysfunction may have an early onset in type 1 diabetes (T1D) and can precede major complications. Our objectives were to assess the endothelial-dependent (acetylcholine, ACh; and post-occlusive hyperemia, PORH), non-endothelial-dependent (sodium nitroprusside, SNP) and neurovascular-dependent (local heating, LH and current induced Vasodilation, CIV) microcirculatory Vasodilation in T1D patients compared with matched control subjects using a laser speckle contrast imager. Seventeen T1D patients - matched with 17 subjects according to age, gender, Body-Mass-Index, and smoking status - underwent macro- and microvascular investigations. The LH early peak assessed the transient receptor potential vanilloid type 1 channels (TRPV1) mediated Vasodilation, whereas the plateau assessed the Nitirc-Oxyde (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways. PORH explored sensory nerves and (EDHF), while CIV assessed sensory nerves (C-fibers) and prostaglandin-mediated Vasodilation. Using neurological investigations, we observed that C-fiber and A-delta fiber functions in T1D patients were similar to control subjects. PORH, CIV, LH peak and plateau Vasodilations were significantly decreased in T1D patients compared to controls, whereas there was no difference between the two groups for ACh and SNP Vasodilations. Neurovascular microcirculatory Vasodilations (C-fibers and TRPV 1-mediated Vasodilations) are impaired in TD1 patients whereas no abnormalities were found using clinical neurological investigations. Clinicaltrials: No. NCT02538120.
Keith Gottesdiener - One of the best experts on this subject based on the ideXlab platform.
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suppression of niacin induced Vasodilation with an antagonist to prostaglandin d2 receptor subtype 1
Clinical Pharmacology & Therapeutics, 2007Co-Authors: Inge De Lepeleire, L A Wenning, T M Crumley, Gary P Oneill, Nicole Michiels, E Vets, John A Wagner, Keith GottesdienerAbstract:Niacin (nicotinic acid) reduces cardiovascular events in patients with dyslipidemia. However, symptoms associated with niacin-induced Vasodilation (e.g., flushing) have limited its use. Laropiprant is a selective antagonist of the prostaglandin D2 receptor subtype 1 (DP1), which may mediate niacin-induced Vasodilation. The aim of this proof-of-concept study was to evaluate the effects of laropiprant (vs placebo) on niacin-induced cutaneous Vasodilation. Coadministration of laropiprant 30, 100, and 300 mg with extended-release (ER) niacin significantly lowered flushing symptom scores (by approximately 50% or more) and also significantly reduced malar skin blood flow measured by laser Doppler perfusion imaging. Laropiprant was effective after multiple doses in reducing symptoms of flushing and attenuating the increased malar skin blood flow induced by ER niacin. In conclusion, the DP1 receptor antagonist laropiprant was effective in suppressing both subjective and objective manifestations of niacin-induced Vasodilation. Clinical Pharmacology & Therapeutics (2007) 81, 849–857. doi:10.1038/sj.clpt.6100180; published online 28 March 2007
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suppression of niacin induced Vasodilation with an antagonist to prostaglandin d2 receptor subtype 1
Clinical Pharmacology & Therapeutics, 2007Co-Authors: Eseng Lai, L A Wenning, T M Crumley, Gary P Oneill, Inge De Lepeleire, Nicole Michiels, E Vets, John A Wagner, Fang Liu, Keith GottesdienerAbstract:Niacin (nicotinic acid) reduces cardiovascular events in patients with dyslipidemia. However, symptoms associated with niacin-induced Vasodilation (e.g., flushing) have limited its use. Laropiprant is a selective antagonist of the prostaglandin D(2) receptor subtype 1 (DP1), which may mediate niacin-induced Vasodilation. The aim of this proof-of-concept study was to evaluate the effects of laropiprant (vs placebo) on niacin-induced cutaneous Vasodilation. Coadministration of laropiprant 30, 100, and 300 mg with extended-release (ER) niacin significantly lowered flushing symptom scores (by approximately 50% or more) and also significantly reduced malar skin blood flow measured by laser Doppler perfusion imaging. Laropiprant was effective after multiple doses in reducing symptoms of flushing and attenuating the increased malar skin blood flow induced by ER niacin. In conclusion, the DP1 receptor antagonist laropiprant was effective in suppressing both subjective and objective manifestations of niacin-induced Vasodilation.
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antagonism of the prostaglandin d2 receptor 1 suppresses nicotinic acid induced Vasodilation in mice and humans
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Kang Cheng, Kathleen M. Metters, Gary P Oneill, Keith Gottesdiener, Eseng Lai, Claudio Sturino, Zhaoyin Wang, Samuel D Wright, Gerard M WatersAbstract:Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous Vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated Vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced Vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous Vasodilation, and DP2−/− mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced Vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2- and NA-induced Vasodilation. NA-induced Vasodilation was also studied in DP1+/+, DP1+/−, and DP1−/− mice; although NA-induced Vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced Vasodilation in male DP−/− mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced Vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans.