Young M A, Vatner D E, Knight D R, Graham R M, Homcy C J, Vatner S F
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
Am J Physiol. 1988 Dec;255(6 Pt 2):H1452-9. doi: 10.1152/ajpheart.1988.255.6.H1452.
We investigated alpha-adrenoceptor subtype distribution in large coronary arteries from both functional and biochemical perspectives. The effects of intracoronary administration of the selective alpha 1-adrenoceptor agonist phenylephrine (0.1-5.0 micrograms/kg ic), of the selective alpha 2-adrenoceptor agonist B-HT 920 (0.1-5.0 micrograms/kg ic), and of the mixed alpha 1 + 2-adrenoceptor agonist norepinephrine (0.01-0.5 micrograms/kg ic) were examined on measurements of left circumflex coronary artery diameter in conscious calves. After beta-adrenergic blockade, equivalent reductions in large coronary artery diameter were observed with phenylephrine (-6.9 +/- 0.7%), B-HT (-5.9 +/- 0.5%), and norepinephrine (-6.0 +/- 0.4%). Phenylephrine-induced constrictions were abolished by prazosin, an alpha 1-selective antagonist, but unaffected by rauwolscine, an alpha 2-selective antagonist. Conversely, the B-HT-induced constriction was abolished by rauwolscine but unaffected by prazosin. Coronary constriction with norepinephrine was attenuated with either prazosin or rauwolscine and abolished by the two antagonists combined. Ligand-binding studies in which [3H]prazosin and [3H]rauwolscine and sarcolemmal membranes were used revealed an alpha 1-adrenoceptor density of 15 +/- 3.1 fmol/mg protein with a dissociation constant (KD) of 0.7 +/- 0.2 nM and an alpha 2-adrenoceptor density of 68 +/- 5.1 fmol/mg protein, with a KD of 7.4 +/- 1.2 nM. Thus large coronary arteries of the calf contain both alpha 1- and alpha 2-adrenoceptor subtypes, each of which elicits constriction of the large coronary artery in the conscious animal.
我们从功能和生化两个角度研究了大冠状动脉中的α-肾上腺素能受体亚型分布。在清醒的小牛身上,检测了冠状动脉内注射选择性α1-肾上腺素能受体激动剂去氧肾上腺素(0.1 - 5.0微克/千克,冠状动脉内注射)、选择性α2-肾上腺素能受体激动剂B-HT 920(0.1 - 5.0微克/千克,冠状动脉内注射)以及混合性α1 + 2-肾上腺素能受体激动剂去甲肾上腺素(0.01 - 0.5微克/千克,冠状动脉内注射)对左旋冠状动脉直径测量值的影响。在β-肾上腺素能阻断后,去氧肾上腺素(-6.9±0.7%)、B-HT(-5.9±0.5%)和去甲肾上腺素(-6.0±0.4%)使大冠状动脉直径出现了等效的减小。去氧肾上腺素引起的收缩可被α1选择性拮抗剂哌唑嗪消除,但不受α2选择性拮抗剂萝芙木碱的影响。相反,B-HT引起的收缩可被萝芙木碱消除,但不受哌唑嗪的影响。去甲肾上腺素引起的冠状动脉收缩可被哌唑嗪或萝芙木碱减弱,并被两种拮抗剂联合使用完全消除。使用[3H]哌唑嗪、[3H]萝芙木碱和肌膜进行的配体结合研究显示,α1-肾上腺素能受体密度为15±3.1飞摩尔/毫克蛋白,解离常数(KD)为0.7±0.2纳摩尔,α2-肾上腺素能受体密度为68±5.1飞摩尔/毫克蛋白,KD为7.4±1.2纳摩尔。因此,小牛的大冠状动脉同时含有α1和α2肾上腺素能受体亚型,每种亚型均可在清醒动物中引起大冠状动脉的收缩。