Davenport A P, Kuc R E, Maguire J J, Harland S P
Clinical Pharmacology Unit, University of Cambridge, Addenbrookes Hospital, England.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S265-7.
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.
我们的目的是确定人类血管中存在哪些内皮素（ET）受体亚型。我们使用亚型选择性放射性标记配体[¹²⁵I]-PD151242和[¹²⁵I]-BQ3020，来测量人类组织（包括脑、肾、心脏、肺和肾上腺）血管中层中内皮素ETA和ETB受体的比例。在脑中，皮质内的阻力血管（直径小于300微米）和软脑膜动脉仅表达ETA受体。在肾中，高密度的ETA受体定位于阻力血管。在较大直径的血管中可检测到少量的ETB受体；ETA:ETB的比例分别为90:10（肾动脉）、92:8（肾静脉）和95:5（弓状动脉）。在心脏中，仅在心肌内阻力血管中可检测到ETA受体。在从动脉粥样硬化患者切除的心外膜冠状动脉和主动脉中发现少量ETB受体（小于15%），但在正常血管中难以检测到ETB受体。在肾上腺中，ETA受体在被膜丛动脉（87:13）、中央髓质静脉（85:15）和阻力血管中也占主导地位。ETB受体在肺动脉、乳内动脉和大隐静脉中也占ET受体的不到15%。结果显示出一种一致的模式，即在这些组织的阻力血管中仅检测到ETA受体。在较大的动脉和静脉中，ETB亚型最多占ET受体的约15%。我们之前在人体动脉和静脉中已表明，ET-1通过ETA亚型介导血管收缩。结果表明，由于未检测到ETB受体，ET-1诱导的收缩在较小的阻力血管中也将通过ETA亚型发生。
