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Rafael F Schafers - One of the best experts on this subject based on the ideXlab platform.
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insulin mediated venodilation is impaired in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Anna Mitchell, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Mutlu Pace, Rafael F SchafersAbstract:Objective A C825T polymorphism has been identified for the gene encoding the G-protein β3 subunit (GNB3). The 825T allele is associated with hypertension and obesity, which in turn are closely linked with resistance to the metabolic and vascular effects of insulin. We hypothesized that venodilation in response to insulin would be impaired in GNB3 825T-allele carriers. Because vasodilatory properties of insulin are mainly mediated by nitric oxide, we also investigated the influence of the T−786C polymorphism of the gene for endothelial nitric oxide synthase (NOS3) on insulin-mediated venous responses. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 31 young, healthy men (GNB3 C825T: 15 CC, 14 CT, and 2 TT; NOS3 T−786C: 14 TT, 13 TC, and 4 CC). Individual dose-response curves to phenylephrine (3.2–10,000 ng/min) were established, and Veins were preconstricted by a constant infusion of phenylephrine at the individual dose needed to procure 70% of maximal constriction. Then insulin was infused (50–250,000 μU/min), and the changes in venous diameter were recorded. Results Venous response to insulin was biphasic, with venoconstriction at low doses being followed by venodilation at higher doses. Insulin dose-response curves of GNB3 825T-allele carriers were significantly shifted to the right (ANOVA, P < .001, versus CC). NOS3 T−786C-allele carrier status had no influence on insulin-induced vascular responses (P = .60 for TC/CC versus TT). Conclusion This study is the first to show the influence of a genetic polymorphism on insulin-mediated venodilation in men in vivo. Further studies are needed to determine whether these results translate to other vascular beds, and possible gender-specific differences remain to be investigated. Clinical Pharmacology & Therapeutics (2005) 77, 495–502; doi: 10.1016/j.clpt.2005.03.002
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venous response to nitroglycerin is enhanced in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2003Co-Authors: Anna Mitchell, Sandra Buhrmann, Anne Seifert, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Rafael F SchafersAbstract:Objective The ultimate mode of action by which nitroglycerin elicits vasodilation remains elusive. Animal studies point to an involvement of pertussis toxin–sensitive G proteins. The 825T allele of the GNB3 C825T polymorphism in the gene encoding the G protein β3 subunit is associated with enhanced signal transduction via pertussis toxin–sensitive pathways in vitro. We hypothesized that G proteins have a role in nitroglycerin-mediated vasodilation and that carriers of the 825T allele would exhibit a stronger response to nitroglycerin. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 28 young, healthy men with and without the T allele (n = 15 CC, n = 8 CT, and n = 5 TT). After individual dose-response curves to phenylephrine had been established, Veins were preconstricted to 70% of the maximal phenylephrine-induced constriction. Nitroglycerin was then infused in ascending doses (0.02–2000 ng/min), and the vasodilatory response was measured. Results The vasodilatory response to nitroglycerin was significantly greater in carriers of the 825T allele. The maximal response to nitroglycerin was 102% ± 6% venodilation in the CT/TT group and 78% ± 5% in the CC control group (P = .0045) (mean difference, −24% ± 8%; 95% confidence interval, 8%-40%). Comparison of the nitroglycerin dose-response curves by ANOVA confirmed an enhanced nitroglycerin-induced venodilation in 825T-allele carriers (P < .0001). Conclusion Our results suggest that the GNB3 C825T polymorphism determines venous response to nitroglycerin and that G proteins may be involved in the signal transduction pathway. Clinical Pharmacology & Therapeutics (2003) 74, 499–504; doi: 10.1016/S0009-9236(03)00230-3
Anna Mitchell - One of the best experts on this subject based on the ideXlab platform.
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insulin mediated venodilation is impaired in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Anna Mitchell, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Mutlu Pace, Rafael F SchafersAbstract:Objective A C825T polymorphism has been identified for the gene encoding the G-protein β3 subunit (GNB3). The 825T allele is associated with hypertension and obesity, which in turn are closely linked with resistance to the metabolic and vascular effects of insulin. We hypothesized that venodilation in response to insulin would be impaired in GNB3 825T-allele carriers. Because vasodilatory properties of insulin are mainly mediated by nitric oxide, we also investigated the influence of the T−786C polymorphism of the gene for endothelial nitric oxide synthase (NOS3) on insulin-mediated venous responses. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 31 young, healthy men (GNB3 C825T: 15 CC, 14 CT, and 2 TT; NOS3 T−786C: 14 TT, 13 TC, and 4 CC). Individual dose-response curves to phenylephrine (3.2–10,000 ng/min) were established, and Veins were preconstricted by a constant infusion of phenylephrine at the individual dose needed to procure 70% of maximal constriction. Then insulin was infused (50–250,000 μU/min), and the changes in venous diameter were recorded. Results Venous response to insulin was biphasic, with venoconstriction at low doses being followed by venodilation at higher doses. Insulin dose-response curves of GNB3 825T-allele carriers were significantly shifted to the right (ANOVA, P < .001, versus CC). NOS3 T−786C-allele carrier status had no influence on insulin-induced vascular responses (P = .60 for TC/CC versus TT). Conclusion This study is the first to show the influence of a genetic polymorphism on insulin-mediated venodilation in men in vivo. Further studies are needed to determine whether these results translate to other vascular beds, and possible gender-specific differences remain to be investigated. Clinical Pharmacology & Therapeutics (2005) 77, 495–502; doi: 10.1016/j.clpt.2005.03.002
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venous response to nitroglycerin is enhanced in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2003Co-Authors: Anna Mitchell, Sandra Buhrmann, Anne Seifert, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Rafael F SchafersAbstract:Objective The ultimate mode of action by which nitroglycerin elicits vasodilation remains elusive. Animal studies point to an involvement of pertussis toxin–sensitive G proteins. The 825T allele of the GNB3 C825T polymorphism in the gene encoding the G protein β3 subunit is associated with enhanced signal transduction via pertussis toxin–sensitive pathways in vitro. We hypothesized that G proteins have a role in nitroglycerin-mediated vasodilation and that carriers of the 825T allele would exhibit a stronger response to nitroglycerin. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 28 young, healthy men with and without the T allele (n = 15 CC, n = 8 CT, and n = 5 TT). After individual dose-response curves to phenylephrine had been established, Veins were preconstricted to 70% of the maximal phenylephrine-induced constriction. Nitroglycerin was then infused in ascending doses (0.02–2000 ng/min), and the vasodilatory response was measured. Results The vasodilatory response to nitroglycerin was significantly greater in carriers of the 825T allele. The maximal response to nitroglycerin was 102% ± 6% venodilation in the CT/TT group and 78% ± 5% in the CC control group (P = .0045) (mean difference, −24% ± 8%; 95% confidence interval, 8%-40%). Comparison of the nitroglycerin dose-response curves by ANOVA confirmed an enhanced nitroglycerin-induced venodilation in 825T-allele carriers (P < .0001). Conclusion Our results suggest that the GNB3 C825T polymorphism determines venous response to nitroglycerin and that G proteins may be involved in the signal transduction pathway. Clinical Pharmacology & Therapeutics (2003) 74, 499–504; doi: 10.1016/S0009-9236(03)00230-3
Thomas Philipp - One of the best experts on this subject based on the ideXlab platform.
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insulin mediated venodilation is impaired in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Anna Mitchell, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Mutlu Pace, Rafael F SchafersAbstract:Objective A C825T polymorphism has been identified for the gene encoding the G-protein β3 subunit (GNB3). The 825T allele is associated with hypertension and obesity, which in turn are closely linked with resistance to the metabolic and vascular effects of insulin. We hypothesized that venodilation in response to insulin would be impaired in GNB3 825T-allele carriers. Because vasodilatory properties of insulin are mainly mediated by nitric oxide, we also investigated the influence of the T−786C polymorphism of the gene for endothelial nitric oxide synthase (NOS3) on insulin-mediated venous responses. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 31 young, healthy men (GNB3 C825T: 15 CC, 14 CT, and 2 TT; NOS3 T−786C: 14 TT, 13 TC, and 4 CC). Individual dose-response curves to phenylephrine (3.2–10,000 ng/min) were established, and Veins were preconstricted by a constant infusion of phenylephrine at the individual dose needed to procure 70% of maximal constriction. Then insulin was infused (50–250,000 μU/min), and the changes in venous diameter were recorded. Results Venous response to insulin was biphasic, with venoconstriction at low doses being followed by venodilation at higher doses. Insulin dose-response curves of GNB3 825T-allele carriers were significantly shifted to the right (ANOVA, P < .001, versus CC). NOS3 T−786C-allele carrier status had no influence on insulin-induced vascular responses (P = .60 for TC/CC versus TT). Conclusion This study is the first to show the influence of a genetic polymorphism on insulin-mediated venodilation in men in vivo. Further studies are needed to determine whether these results translate to other vascular beds, and possible gender-specific differences remain to be investigated. Clinical Pharmacology & Therapeutics (2005) 77, 495–502; doi: 10.1016/j.clpt.2005.03.002
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venous response to nitroglycerin is enhanced in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2003Co-Authors: Anna Mitchell, Sandra Buhrmann, Anne Seifert, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Rafael F SchafersAbstract:Objective The ultimate mode of action by which nitroglycerin elicits vasodilation remains elusive. Animal studies point to an involvement of pertussis toxin–sensitive G proteins. The 825T allele of the GNB3 C825T polymorphism in the gene encoding the G protein β3 subunit is associated with enhanced signal transduction via pertussis toxin–sensitive pathways in vitro. We hypothesized that G proteins have a role in nitroglycerin-mediated vasodilation and that carriers of the 825T allele would exhibit a stronger response to nitroglycerin. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 28 young, healthy men with and without the T allele (n = 15 CC, n = 8 CT, and n = 5 TT). After individual dose-response curves to phenylephrine had been established, Veins were preconstricted to 70% of the maximal phenylephrine-induced constriction. Nitroglycerin was then infused in ascending doses (0.02–2000 ng/min), and the vasodilatory response was measured. Results The vasodilatory response to nitroglycerin was significantly greater in carriers of the 825T allele. The maximal response to nitroglycerin was 102% ± 6% venodilation in the CT/TT group and 78% ± 5% in the CC control group (P = .0045) (mean difference, −24% ± 8%; 95% confidence interval, 8%-40%). Comparison of the nitroglycerin dose-response curves by ANOVA confirmed an enhanced nitroglycerin-induced venodilation in 825T-allele carriers (P < .0001). Conclusion Our results suggest that the GNB3 C825T polymorphism determines venous response to nitroglycerin and that G proteins may be involved in the signal transduction pathway. Clinical Pharmacology & Therapeutics (2003) 74, 499–504; doi: 10.1016/S0009-9236(03)00230-3
Winfried Siffert - One of the best experts on this subject based on the ideXlab platform.
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insulin mediated venodilation is impaired in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Anna Mitchell, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Mutlu Pace, Rafael F SchafersAbstract:Objective A C825T polymorphism has been identified for the gene encoding the G-protein β3 subunit (GNB3). The 825T allele is associated with hypertension and obesity, which in turn are closely linked with resistance to the metabolic and vascular effects of insulin. We hypothesized that venodilation in response to insulin would be impaired in GNB3 825T-allele carriers. Because vasodilatory properties of insulin are mainly mediated by nitric oxide, we also investigated the influence of the T−786C polymorphism of the gene for endothelial nitric oxide synthase (NOS3) on insulin-mediated venous responses. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 31 young, healthy men (GNB3 C825T: 15 CC, 14 CT, and 2 TT; NOS3 T−786C: 14 TT, 13 TC, and 4 CC). Individual dose-response curves to phenylephrine (3.2–10,000 ng/min) were established, and Veins were preconstricted by a constant infusion of phenylephrine at the individual dose needed to procure 70% of maximal constriction. Then insulin was infused (50–250,000 μU/min), and the changes in venous diameter were recorded. Results Venous response to insulin was biphasic, with venoconstriction at low doses being followed by venodilation at higher doses. Insulin dose-response curves of GNB3 825T-allele carriers were significantly shifted to the right (ANOVA, P < .001, versus CC). NOS3 T−786C-allele carrier status had no influence on insulin-induced vascular responses (P = .60 for TC/CC versus TT). Conclusion This study is the first to show the influence of a genetic polymorphism on insulin-mediated venodilation in men in vivo. Further studies are needed to determine whether these results translate to other vascular beds, and possible gender-specific differences remain to be investigated. Clinical Pharmacology & Therapeutics (2005) 77, 495–502; doi: 10.1016/j.clpt.2005.03.002
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venous response to nitroglycerin is enhanced in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2003Co-Authors: Anna Mitchell, Sandra Buhrmann, Anne Seifert, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Rafael F SchafersAbstract:Objective The ultimate mode of action by which nitroglycerin elicits vasodilation remains elusive. Animal studies point to an involvement of pertussis toxin–sensitive G proteins. The 825T allele of the GNB3 C825T polymorphism in the gene encoding the G protein β3 subunit is associated with enhanced signal transduction via pertussis toxin–sensitive pathways in vitro. We hypothesized that G proteins have a role in nitroglycerin-mediated vasodilation and that carriers of the 825T allele would exhibit a stronger response to nitroglycerin. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 28 young, healthy men with and without the T allele (n = 15 CC, n = 8 CT, and n = 5 TT). After individual dose-response curves to phenylephrine had been established, Veins were preconstricted to 70% of the maximal phenylephrine-induced constriction. Nitroglycerin was then infused in ascending doses (0.02–2000 ng/min), and the vasodilatory response was measured. Results The vasodilatory response to nitroglycerin was significantly greater in carriers of the 825T allele. The maximal response to nitroglycerin was 102% ± 6% venodilation in the CT/TT group and 78% ± 5% in the CC control group (P = .0045) (mean difference, −24% ± 8%; 95% confidence interval, 8%-40%). Comparison of the nitroglycerin dose-response curves by ANOVA confirmed an enhanced nitroglycerin-induced venodilation in 825T-allele carriers (P < .0001). Conclusion Our results suggest that the GNB3 C825T polymorphism determines venous response to nitroglycerin and that G proteins may be involved in the signal transduction pathway. Clinical Pharmacology & Therapeutics (2003) 74, 499–504; doi: 10.1016/S0009-9236(03)00230-3
Jens Nurnberger - One of the best experts on this subject based on the ideXlab platform.
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insulin mediated venodilation is impaired in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Anna Mitchell, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Mutlu Pace, Rafael F SchafersAbstract:Objective A C825T polymorphism has been identified for the gene encoding the G-protein β3 subunit (GNB3). The 825T allele is associated with hypertension and obesity, which in turn are closely linked with resistance to the metabolic and vascular effects of insulin. We hypothesized that venodilation in response to insulin would be impaired in GNB3 825T-allele carriers. Because vasodilatory properties of insulin are mainly mediated by nitric oxide, we also investigated the influence of the T−786C polymorphism of the gene for endothelial nitric oxide synthase (NOS3) on insulin-mediated venous responses. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 31 young, healthy men (GNB3 C825T: 15 CC, 14 CT, and 2 TT; NOS3 T−786C: 14 TT, 13 TC, and 4 CC). Individual dose-response curves to phenylephrine (3.2–10,000 ng/min) were established, and Veins were preconstricted by a constant infusion of phenylephrine at the individual dose needed to procure 70% of maximal constriction. Then insulin was infused (50–250,000 μU/min), and the changes in venous diameter were recorded. Results Venous response to insulin was biphasic, with venoconstriction at low doses being followed by venodilation at higher doses. Insulin dose-response curves of GNB3 825T-allele carriers were significantly shifted to the right (ANOVA, P < .001, versus CC). NOS3 T−786C-allele carrier status had no influence on insulin-induced vascular responses (P = .60 for TC/CC versus TT). Conclusion This study is the first to show the influence of a genetic polymorphism on insulin-mediated venodilation in men in vivo. Further studies are needed to determine whether these results translate to other vascular beds, and possible gender-specific differences remain to be investigated. Clinical Pharmacology & Therapeutics (2005) 77, 495–502; doi: 10.1016/j.clpt.2005.03.002
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venous response to nitroglycerin is enhanced in young healthy carriers of the 825t allele of the g protein β3 subunit gene gnb3
Clinical Pharmacology & Therapeutics, 2003Co-Authors: Anna Mitchell, Sandra Buhrmann, Anne Seifert, Jens Nurnberger, Rene R Wenzel, Winfried Siffert, Thomas Philipp, Rafael F SchafersAbstract:Objective The ultimate mode of action by which nitroglycerin elicits vasodilation remains elusive. Animal studies point to an involvement of pertussis toxin–sensitive G proteins. The 825T allele of the GNB3 C825T polymorphism in the gene encoding the G protein β3 subunit is associated with enhanced signal transduction via pertussis toxin–sensitive pathways in vitro. We hypothesized that G proteins have a role in nitroglycerin-mediated vasodilation and that carriers of the 825T allele would exhibit a stronger response to nitroglycerin. Methods We used the linear variable transducer technique to compare dorsal hand Vein Compliance in 28 young, healthy men with and without the T allele (n = 15 CC, n = 8 CT, and n = 5 TT). After individual dose-response curves to phenylephrine had been established, Veins were preconstricted to 70% of the maximal phenylephrine-induced constriction. Nitroglycerin was then infused in ascending doses (0.02–2000 ng/min), and the vasodilatory response was measured. Results The vasodilatory response to nitroglycerin was significantly greater in carriers of the 825T allele. The maximal response to nitroglycerin was 102% ± 6% venodilation in the CT/TT group and 78% ± 5% in the CC control group (P = .0045) (mean difference, −24% ± 8%; 95% confidence interval, 8%-40%). Comparison of the nitroglycerin dose-response curves by ANOVA confirmed an enhanced nitroglycerin-induced venodilation in 825T-allele carriers (P < .0001). Conclusion Our results suggest that the GNB3 C825T polymorphism determines venous response to nitroglycerin and that G proteins may be involved in the signal transduction pathway. Clinical Pharmacology & Therapeutics (2003) 74, 499–504; doi: 10.1016/S0009-9236(03)00230-3
