Garrison E A, Santiago J A, Osei S Y, Kadowitz P J
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Physiol. 1995 Jun;268(6 Pt 2):H2418-25. doi: 10.1152/ajpheart.1995.268.6.H2418.
Responses to angiotensin I, II, III, and IV, des-Asp1-angiotensin I, and (p-amino-Phe6)-angiotensin II were compared in the hindquarters vascular bed of the cat. The peptides produced dose-related increases in perfusion pressure, and dose-response curves to all six peptides were parallel. Des-Asp1-angiotensin I, angiotensin I, II, and III produced similar increases in perfusion pressure and were approximately 300-fold more potent than (p-amino-Phe6)-angiotensin II, 100-fold more potent than angiotensin IV, 30-fold more potent than norepinephrine, and 10-fold more potent than U-46619. The time courses of the response to des-Asp1-angiotensin I, angiotensin I, II, and III were similar, and responses were not altered by a time-delay coil. DuP-532, an AT1 receptor antagonist, reduced responses to the six angiotensin peptides. PD-123,319 did not alter responses to the angiotensin peptides. The angiotensin-converting enzyme inhibitor captopril reduced responses to angiotensin I and des-Asp1-angiotensin I. These results show that des-Asp1-angiotensin I as well as angiotensin I, II, III, and IV have similar efficacy and that responses to the peptides and (p-amino-Phe6)-angiotensin II are mediated by AT1 receptors. These results suggest that AT2 receptors have little role in modulating responses and that angiotensin IV has a lower affinity for the AT1 receptor than does angiotensin II or III. The results also indicate that complete rapid local conversion of the substrates into active peptides occurs near the site of action within the hindquarters vascular bed.
在猫的后肢血管床中比较了对血管紧张素I、II、III和IV、去天冬氨酸1 -血管紧张素I以及（对氨基苯丙氨酸6）-血管紧张素II的反应。这些肽类可使灌注压呈剂量依赖性升高，并且所有六种肽的剂量 - 反应曲线是平行的。去天冬氨酸1 -血管紧张素I、血管紧张素I、II和III引起的灌注压升高相似，其效力比（对氨基苯丙氨酸6）-血管紧张素II高约300倍，比血管紧张素IV高100倍，比去甲肾上腺素高30倍，比U - 46619高10倍。对去天冬氨酸1 -血管紧张素I、血管紧张素I、II和III的反应时间进程相似，并且反应不受延时线圈的影响。AT1受体拮抗剂DuP - 532可降低对六种血管紧张素肽的反应。PD - 123319不改变对血管紧张素肽的反应。血管紧张素转换酶抑制剂卡托普利可降低对血管紧张素I和去天冬氨酸1 -血管紧张素I的反应。这些结果表明，去天冬氨酸1 -血管紧张素I以及血管紧张素I、II、III和IV具有相似的效力，并且对这些肽和（对氨基苯丙氨酸6）-血管紧张素II的反应是由AT1受体介导的。这些结果表明，AT2受体在调节反应中作用很小，并且血管紧张素IV对AT1受体的亲和力低于血管紧张素II或III。结果还表明，底物在作用部位附近的后肢血管床内完全快速地局部转化为活性肽。
