Mirabegron relaxes arteries from human visceral adipose tissue through antagonism of α-adrenergic receptors.

AIM

As inadequate perfusion has emerged as a key determinant of adipose tissue dysfunction in obesity, interest has grown regarding possible pharmacological interventions to prevent this process. Mirabegron has proved to improve insulin sensitivity and glucose homeostasis in obese humans via stimulation of β-adrenoceptors which also seem to mediate endothelium-dependent vasodilation in disparate human vascular beds. We characterized, therefore, the vasomotor function of mirabegron in human adipose tissue arteries and the underlying mechanisms.

METHODS

Small arteries (116-734 μm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. After vessels had been contracted, changes in vascular tone in response to mirabegron were determined under different conditions.

RESULTS

Mirabegron did not elicit vasorelaxation in vessels contracted with U46619 or high-K (both P > 0.05). Notably, mirabegron markedly blunted the contractile effect of the α-adrenergic receptor agonist phenylephrine (P < 0.001) either in presence or absence of the vascular endothelium. The anti-contractile action of mirabegron on phenylephrine-induced vasoconstriction was not influenced by the presence of the selective β-adrenoceptor blocker L-748,337 (P < 0.05); lack of involvement of β-adrenoceptors was further supported by absent vascular staining for them at immunohistochemistry.

CONCLUSIONS

Mirabegron induces endothelium-independent vasorelaxation in arteries from visceral adipose tissue, likely through antagonism of α-adrenoceptors.

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