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J Cardiovasc Pharmacol ; 83(6): 621-634, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38547520

ABSTRACT

ABSTRACT: Type 2 diabetes mellitus increases the risk of cardiovascular diseases. Therefore, elucidation of the cardiovascular effects of antidiabetics is crucial. Incretin-based therapies are increasingly used for type 2 diabetes mellitus treatment as monotherapy and in combination. We aimed to study the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sitagliptin on beating rates in isolated atria from diabetic rats. The chronotropic responses to GLP-1 RAs and sitagliptin as monotherapy and in combinations with metformin, pioglitazone, and glimepiride in isolated atria from control and diabetic rats were determined. GLP-1 (7-36), GLP-1 (9-36), and exendin-4 (1-39) produced increases in beating rates in both control and diabetic rat atria. However, sitagliptin increased the beating frequency only in the diabetic group. Exendin (9-39), nitro- l -arginine methyl ester hydrochloride, and indomethacin blocked responses to GLP-1 RAs but not the response to sitagliptin. Glibenclamide, 4-aminopyridine, apamin, charybdotoxin, superoxide dismutase, and catalase incubations did not change responses to GLP-1 RAs and sitagliptin. GLP-1 RAs increase beating rates in isolated rat atrium through GLP-1 receptor, nitric oxide, and cyclooxygenase pathways but not potassium channels and reactive oxygen radicals.


Subject(s)
Diabetes Mellitus, Experimental , Glucagon-Like Peptide-1 Receptor , Heart Atria , Heart Rate , Hypoglycemic Agents , Sitagliptin Phosphate , Animals , Sitagliptin Phosphate/pharmacology , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Male , Heart Atria/drug effects , Heart Atria/physiopathology , Heart Atria/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/physiopathology , Heart Rate/drug effects , Hypoglycemic Agents/pharmacology , Rats , Rats, Wistar , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/metabolism , Exenatide/pharmacology , Incretins/pharmacology , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptide 1/metabolism , Pyrazines/pharmacology , Glucagon-Like Peptide-1 Receptor Agonists
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