Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway
| Autor: | Karina B. Balestrasse, Susana Gorzalczany, Ariel H. Polizio, Diego M. Santa-Cruz, Facundo Martín Bertera, Carlos A. Taira, Chistian Höcht |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Drug Evaluation Preclinical Blood Pressure Pharmacology Second Messenger Systems Biochemistry Nebivolol Rats Sprague-Dawley chemistry.chemical_compound ANTIOXIDANTS Heart Rate Enos OXIDATIVE STRESS Cyclic GMP CARDIOVASCULAR THERAPEUTIC Aorta chemistry.chemical_classification biology Superoxide Drug Synergism Free Radical Scavengers purl.org/becyt/ford/3.1 [https] General Medicine THIRD GENERATION BETA BLOCKERS Nitric oxide synthase Medicina Básica Ethanolamines Hypertension Drug Therapy Combination purl.org/becyt/ford/3 [https] NITRIC OXIDE medicine.drug Farmacología y Farmacia CIENCIAS MÉDICAS Y DE LA SALUD Nitric Oxide Synthase Type III Nitric Oxide Nitric oxide Cyclic N-Oxides medicine Animals Benzopyrans Cyclic guanosine monophosphate Antihypertensive Agents Reactive oxygen species NADPH Oxidases biology.organism_classification Rats Oxidative Stress chemistry Guanylate Cyclase biology.protein Spin Labels Lipid Peroxidation ENDOTHELIAL NITRIC OXIDE Reactive Oxygen Species cGMP-dependent protein kinase |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 1029-2470 1071-5762 |
| Popis: | Nebivolol is a third generation beta blocker with endothelial nitric oxide synthase (eNOS) agonist properties. Considering the role of reactive oxygen species (ROS) in the uncoupling of eNOS, we hypothesized that the preadministration of an antioxidant as tempol, could improve the hypotensive response of nebivolol in normotensive animals increasing the nitric oxide (NO) bioavailability by a reduction of superoxide (O2•−) basal level production in the vascular tissue. Male Sprague Dawley rats were given tap water to drink (control group) or tempol (an antioxidant scavenger of superoxide) for 1 week. After 1 week, Nebivolol, at a dose of 3 mg/kg, was injected intravenously to the control group or to the tempol-treated group. Mean arterial pressure, heart rate, and blood pressure variability were evaluated in the control, tempol, nebivolol, and tempol nebivolol groups, as well as, the effect of different inhibitor as Nβ-nitro-l-arginine methyl ester (L-NAME, a Nitric oxide synthase blocker) or glybenclamide, a KATP channel inhibitor. Also, the expression of α,β soluble guanylate cyclase (sGC), phospho-eNOS, and phospho-vasodilator-stimulated phosphoprotein (P-VASP) were evaluated by Western Blot and cyclic guanosine monophosphate (cGMP) levels by an enzyme-linked immunosorbent assay (ELISA) commercial kit assay. We showed that pretreatment with tempol in normotensive rats produces a hypotensive response after nebivolol administration through an increase in the NO bioavailability and sGC, improving the NO/cGMP/protein kinase G (PKG) pathway compared to that of the nebivolol group. We demonstrated that tempol preadministration beneficiates the response of a third-generation beta blocker with eNOS stimulation properties, decreasing the basal uncoupling of eNOS, and improving NO bioavailability. Our results clearly open a possible new strategy therapeutic for treating hypertension. Fil: Bertera, Facundo Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina Fil: Santa Cruz, Diego Mario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Balestrasse, Karina Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gorzalczany, Susana Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Polizio, Ariel Héctor. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
| Databáze: | OpenAIRE |
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