Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells

Alpha-1-adrenergic receptors (alpha 1-ARs) regulate coronary arterial blood flow by binding catecholamines, norepinephrine (NE), and epinephrine (EPI), causing vasoconstriction when the endothelium is disrupted. Among the three alpha 1-AR subtypes (alpha 1A, alpha 1B, and alpha 1D), the alpha 1D subtype predominates in human epicardial coronary arteries and is functional in human coronary smooth muscle cells (SMCs). However, the presence or function of alpha 1-ARs on human coronary endothelial cells (ECs) is unknown. Here we tested the hypothesis that human epicardial coronary ECs express functional alpha 1-ARs. Cultured human epicardial coronary artery ECs were studied using quantitative real-time reverse transcription polymerase chain reaction, radioligand binding, immunoblot, and H-3-thymidine incorporation. The alpha 1B-subtype messenger ribonucleic acid (mRNA) was predominant in cultured human epicardial coronary ECs (90-95% of total alpha 1-AR mRNA), and total alpha 1-AR binding density in ECs was twice that in coronary SMCs. Functionally, NE and EPI through the alpha 1B subtype activated extracellular signal-regulated kinase (ERK) in ECs, stimulated phosphorylation of EC endothelial nitric oxide synthase (eNOS), and increased deoxyribonucleic acid (DNA) synthesis. These results are the first to demonstrate alpha 1-ARs on human coronary ECs and indicate that the alpha 1B subtype is predominant. Our findings provide another potential mechanism for adverse cardiac effects of drug antagonists that nonselectively inhibit all three alpha 1-AR subtypes.