Mirabegron is the first ß₃ adrenoreceptor agonist drug that is licensed for the management of overactive bladder. It has also been recently introduced as a potential therapeutic mean for obesity. However, its effects on cardiovascular function of spontaneously hypertensive rats (SHR) with metabolic syndrome are not well known so far.

The aim of this study was to investigate the effects of a long-term administration of mirabegron on cardiovascular reactivity in SHR rats with an induced metabolic syndrome.

Twenty-four 9-week-old rats were randomly divided into 3 groups: control group, cafeteria diet fed group and cafeteria diet fed group receiving a daily oral dose of mirabegron (5mg/kg) for 12 weeks. Measurments of body weight, abdominal circumference, blood pressure and glucose tolerance test were performed. Cumulative concentration-response curves to isoprenaline (0.1nM–1μM), acetylcholine (1nM–10μM) and phenylephrine (1nM–10μM) were determined on isolated perfused heart and thoracic aorta. cGMP assays were performed on heart and thoracic aorta samples.

The results revealed that 12 weeks of cafeteria diet induced the typical signs of the metabolic syndrome in cafeteria diet fed group. These metabolic alterations were associated with a decrease in ß-adrenoceptor-induced cardiac inotropy and coronary perfusion as well as an alteration of α₁-adrenergic response. However, no difference in acetylcholine-mediated vasorelaxation was detected between groups. Similarly, intracellular cGMP levels showed no significant difference between treated and untreated animals. Mirabegron chronic treatment significantly improved the in vivo measured parameters, slightly restored the α₁-adrenergic-induced vasoconstriction and the cardiac contractility.

The main results showed protective cardiovascular effects of mirabegron, making ß₃-adrenergic receptor activation a promising option to consider during metabolic syndrome.