ETA receptors predominate in the human vasculature and mediate constriction

Our aim was to identify which endothelin (ET) receptor subtypes are present in the human vasculature. We used subtype-selective radiolabeled ligands, [125I]-PD151242 and [125I]-BQ3020, to measure the ratio of endothelin ETA and ETB receptors in the media of blood vessels in human tissues including brain, kidney, heart, lung, and adrenal. In the brain, resistance vessels (diameter less than 300 micron) within the cortex and the pial arteries expressed only ETA receptors. In the kidney, high densities of ETA receptors were localized to the resistance vessels. A small population of ETB receptors was detectable in larger diameter vessels; the ratios of ETA: ETB were 90:10 (renal artery), 92:8 (renal vein), and 95:5 (arcuate artery). In the heart, only ETA receptors could be detected within intramyocardial resistance vessels. A small number of ETB receptors (less than 15%) were found in epicardial coronary arteries and aorta removed from patients with atherosclerosis, but ETB receptors were difficult to detect in normal vessels. In the adrenal, ETA receptors also predominated in arteries of the capsular plexus (87:13), central medullary vein (85:15), and resistance vessels. ETB receptors also represented less than 15% of the ET receptors in the pulmonary artery, internal mammary artery, and saphenous vein. The results show a consistent pattern, with only ETA receptors detected in resistance vessels in these tissues. In the larger arteries and veins, the ETB subtype represents a maximum of about 15% of the ET receptors. We have previously shown in human arteries and veins that ET-1 mediates vasoconstriction via the ETA subtype. The results suggest that ET-1-induced constriction would also occur via the ETA subtype in the smaller resistance vessels, as ETB receptors could not be detected.