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Start Over Descriptor "β3 adrenergic receptors" Journal journal of the american heart association
2 results on '"β3 adrenergic receptors"'

1. β3 Adrenergic Stimulation Restores Nitric Oxide/Redox Balance and Enhances Endothelial Function in Hyperglycemia

Author

N. Fry, Keyvan Karimi Galougahi, Alvaro Garcia, Clare L. Hawkins, Elisha J. Hamilton, Carmine Gentile, Gemma A. Figtree, and Chia-Chi Liu

Subjects
0301 basic medicine, Blood Glucose, Male, Time Factors, 030204 cardiovascular system & hematology, medicine.disease_cause, Vascular Medicine, endothelial dysfunction, chemistry.chemical_compound, 0302 clinical medicine, Enos, Superoxides, oxidative stress, Endothelial dysfunction, Original Research, NADPH oxidase, biology, Nitric Oxide Synthase Type III, Glutathione, Endothelium/Vascular Type/Nitric Oxide, Rabbits, Sodium-Potassium-Exchanging ATPase, Cardiology and Cardiovascular Medicine, Oxidation-Reduction, Signal Transduction, medicine.medical_specialty, Adrenergic receptor, Adrenergic beta-3 Receptor Agonists, Dioxoles, Nitric Oxide, Nitric oxide, Diabetes Mellitus, Experimental, 03 medical and health sciences, Vascular Biology, Internal medicine, medicine, Animals, Hypoglycemic Agents, β3 adrenergic receptors, endothelial nitric oxide synthase, Dose-Response Relationship, Drug, business.industry, NADPH Oxidases, medicine.disease, biology.organism_classification, Enzyme Activation, Insulin receptor, 030104 developmental biology, Endocrinology, chemistry, Animal Models of Human Disease, Hyperglycemia, Receptors, Adrenergic, beta-3, biology.protein, Endothelium, Vascular, business, Peptides, Oxidant Stress, Oxidative stress, Diabetic Angiopathies
Abstract

Background Perturbed balance between NO and O 2 •− . (ie, NO/redox imbalance) is central in the pathobiology of diabetes‐induced vascular dysfunction. We examined whether stimulation of β 3 adrenergic receptors (β 3 ARs), coupled to endothelial nitric oxide synthase (eNOS) activation, would re‐establish NO/redox balance, relieve oxidative inhibition of the membrane proteins eNOS and Na + ‐K + (NK) pump, and improve vascular function in a new animal model of hyperglycemia. Methods and Results We established hyperglycemia in male White New Zealand rabbits by infusion of S961, a competitive high‐affinity peptide inhibitor of the insulin receptor. Hyperglycemia impaired endothelium‐dependent vasorelaxation by “uncoupling” of eNOS via glutathionylation (eNOS‐GSS) that was dependent on NADPH oxidase activity. Accordingly, NO levels were lower while O 2 •− levels were higher in hyperglycemic rabbits. Infusion of the β 3 AR agonist CL316243 (CL) decreased eNOS‐GSS, reduced O 2 •− , restored NO levels, and improved endothelium‐dependent relaxation. CL decreased hyperglycemia‐induced NADPH oxidase activation as suggested by co‐immunoprecipitation experiments, and it increased eNOS co‐immunoprecipitation with glutaredoxin‐1, which may reflect promotion of eNOS de‐glutathionylation by CL. Moreover, CL reversed hyperglycemia‐induced glutathionylation of the β 1 NK pump subunit that causes NK pump inhibition, and improved K + ‐induced vasorelaxation that reflects enhancement in NK pump activity. Lastly, eNOS‐GSS was higher in vessels of diabetic patients and was reduced by CL, suggesting potential significance of the experimental findings in human diabetes. Conclusions β 3 AR activation restored NO/redox balance and improved endothelial function in hyperglycemia. β 3 AR agonists may confer protection against diabetes‐induced vascular dysfunction.

Published
2016

2. β3 Adrenergic Stimulation Restores Nitric Oxide/Redox Balance and Enhances Endothelial Function in Hyperglycemia.

Author

Karimi Galougahi K, Liu CC, Garcia A, Gentile C, Fry NA, Hamilton EJ, Hawkins CL, and Figtree GA

Subjects
Animals, Blood Glucose drug effects, Blood Glucose metabolism, Diabetes Mellitus, Experimental chemically induced, Diabetes Mellitus, Experimental enzymology, Diabetes Mellitus, Experimental physiopathology, Diabetic Angiopathies chemically induced, Diabetic Angiopathies enzymology, Diabetic Angiopathies physiopathology, Dose-Response Relationship, Drug, Endothelium, Vascular enzymology, Endothelium, Vascular physiopathology, Enzyme Activation, Glutathione metabolism, Hyperglycemia chemically induced, Hyperglycemia enzymology, Hyperglycemia physiopathology, Male, NADPH Oxidases metabolism, Nitric Oxide Synthase Type III metabolism, Oxidation-Reduction, Oxidative Stress drug effects, Peptides, Rabbits, Receptors, Adrenergic, beta-3 metabolism, Signal Transduction drug effects, Sodium-Potassium-Exchanging ATPase metabolism, Superoxides metabolism, Time Factors, Adrenergic beta-3 Receptor Agonists pharmacology, Diabetes Mellitus, Experimental drug therapy, Diabetic Angiopathies prevention & control, Dioxoles pharmacology, Endothelium, Vascular drug effects, Hyperglycemia drug therapy, Hypoglycemic Agents pharmacology, Nitric Oxide metabolism, Receptors, Adrenergic, beta-3 drug effects
Abstract

Background: Perturbed balance between NO and O2 (•-). (ie, NO/redox imbalance) is central in the pathobiology of diabetes-induced vascular dysfunction. We examined whether stimulation of β3 adrenergic receptors (β3 ARs), coupled to endothelial nitric oxide synthase (eNOS) activation, would re-establish NO/redox balance, relieve oxidative inhibition of the membrane proteins eNOS and Na(+)-K(+) (NK) pump, and improve vascular function in a new animal model of hyperglycemia., Methods and Results: We established hyperglycemia in male White New Zealand rabbits by infusion of S961, a competitive high-affinity peptide inhibitor of the insulin receptor. Hyperglycemia impaired endothelium-dependent vasorelaxation by "uncoupling" of eNOS via glutathionylation (eNOS-GSS) that was dependent on NADPH oxidase activity. Accordingly, NO levels were lower while O2 (•-) levels were higher in hyperglycemic rabbits. Infusion of the β3 AR agonist CL316243 (CL) decreased eNOS-GSS, reduced O2 (•-), restored NO levels, and improved endothelium-dependent relaxation. CL decreased hyperglycemia-induced NADPH oxidase activation as suggested by co-immunoprecipitation experiments, and it increased eNOS co-immunoprecipitation with glutaredoxin-1, which may reflect promotion of eNOS de-glutathionylation by CL. Moreover, CL reversed hyperglycemia-induced glutathionylation of the β1 NK pump subunit that causes NK pump inhibition, and improved K(+)-induced vasorelaxation that reflects enhancement in NK pump activity. Lastly, eNOS-GSS was higher in vessels of diabetic patients and was reduced by CL, suggesting potential significance of the experimental findings in human diabetes., Conclusions: β3 AR activation restored NO/redox balance and improved endothelial function in hyperglycemia. β3 AR agonists may confer protection against diabetes-induced vascular dysfunction., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Published
2016
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