The function of β3‐adrenergic receptors in resistance‐sized arteries

Abstract

Beta‐adrenergic receptors, including the β1, β2, and β3‐adrenergic receptors, are a component of the adrenergic nervous system, with significant expression identified in cardiac, airway smooth muscle, and adipose tissue, respectively. An elevated stimulation of the beta‐adrenergic system has been linked to a variety of cardiovascular complications, including hypertension, heart failure, and cardiac myocyte injury. Upregulation of the β3‐adrenergic receptor is observed in patients with heart failure, and it has been proposed that β3‐adrenergic receptor agonists may potentially be utilized therapeutically to treat the disease. However, little is understood about the function of β3‐adrenergic receptors in systemic resistance‐sized arteries that regulate blood pressure, and whether their expression is altered in cardiovascular diseases, such as hypertension. Simple Western indicates that β3‐adrenergic receptor expression is elevated in resistance‐sized mesenteric and hindlimb arteries isolated from hypertensive C57BL/6J mice, compared to controls. Immunofluorescence of en face mesenteric artery segments reveals expression of β3‐adrenergic receptors in both vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). The β3‐adrenergic receptor agonists mirabegron and L‐755,507 cause vasodilation in cannulated 2nd‐ and 3rd‐order mesenteric artery segments after they have developed myogenic tone at physiological pressure (80 mmHg). These data suggest that β3‐adrenergic receptors regulate arterial tone in systemic resistance‐sized arteries and receptor activation may attenuate elevated vasoconstriction observed in hypertension.