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- W4387621132 abstract "The search for alternative strategies for treatment of cardiovascular diseases, lead to the design and synthesis of N -acylhydrazone derivative, named LASSBio-2062, which is a new ligand of adenosine receptor and that is a possible therapeutic target to reduce blood pressure because of its vasodilatory action and antioxidant properties. This work investigated the effects of a new A 3 adenosine receptor agonist (LASSBio-2062) in spontaneously hypertensive rats (SHR). Animal Care and Use Committee at Universidade Federal do Rio de Janeiro approved the protocols (017/19). Vascular reactivity was evaluated using isometric tension recording of pre-contracted thoracic aorta from male Wistar rats after exposure to increasing concentrations of LASSBio-2062 (0.1 - 100 μM) in the absence or presence of antagonist of adenosine A 2A receptor, ZM-241385 (0.1 μM), an antagonist of adenosine A 3 receptor, MRE 3008F20 (0.1 μM), a blocker of K ATP channel, glibenclamide (10 μM), an inhibitor of Kv channels, 4-AP, inhibitor of BK Ca , TEA (3 mM). Mechanical removal of endothelium increased the EC 50 for vasodilation from 15.5 ± 6.5 to 49.4 ± 10.0 μM, indicating partial dependence on the functional integrity of vascular endothelium. Vascular relaxation was not altered by ZM-241385 but the concentration-response curve shifted to the right with MRE 3008F20 and reduced maximum relaxation from 72.1 ± 4.0 to 23.6 ± 7.7%, indicating that vasodilation occurred by activation of the adenosine receptor type A 3 , but not A 2A . Reduced maximum vascular response by glibenclamide, TEA and 4-AP suggests that activation of A 3 adenosine receptor promotes hyperpolarization as a result reduces intracellular calcium. Antihypertensive effect was investigated in spontaneously hypertensive rats (SHR, 12-15 wks old), through the measurement of mean blood pressure (MBP) after intravenous injection of 10 and 30 μmol/kg of LASSBio-2062. After intravenous administration of LASSBio-2062 (10 umol/kg) in SHR, systolic and diastolic pressures reduced from 155.1 ± 10.1 to 110.6 ± 8.0 and from 111.0 ± 9.1 to 63.9 ± 14.7 mmHg, respectively. HR was also changed from 248.1 ± 12.1 to 146.5 ± 21.0 bpm. In conclusion, the N -acylhydrazone, LASSBio-2062 is a potential therapeutic agent to treat arterial hypertension." @default.
- W4387621132 created "2023-10-14" @default.
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- W4387621132 date "2023-08-04" @default.
- W4387621132 modified "2023-10-15" @default.
- W4387621132 title "Abstract P2142: Evaluation Of Novel A3 Adenosine Receptor Agonist In Hypertension" @default.
- W4387621132 doi "https://doi.org/10.1161/res.133.suppl_1.p2142" @default.
- W4387621132 hasPublicationYear "2023" @default.
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