Gunaruwan Prasad, Maher Abdul, Williams Lynne, Sharman James, Schmitt Matthias, Campbell Ross, Frenneaux Michael
Department of Cardiovascular Medicine, Medical School, University of Birmingham, Edgbaston, UK.
Clin Sci (Lond). 2009 Mar;116(5):443-50. doi: 10.1042/CS20080096.
In the present study, we investigated the effects of basal and intra-arterial infusion of bradykinin on unstressed forearm vascular volume (a measure of venous tone) and blood flow in healthy volunteers (n=20) and in chronic heart failure patients treated with ACEIs [ACE (angiotensin-converting enzyme) inhibitors] (n=16) and ARBs (angiotensin receptor blockers) (n=14). We used radionuclide plethysmography to examine the effects of bradykinin and of the bradykinin antagonists B9340 [B1 (type 1)/B2 (type 2) receptor antagonist] and HOE140 (B2 antagonist). Bradykinin infusion increased unstressed forearm vascular volume in a similar dose-dependent manner in healthy volunteers and ARB-treated CHF patients (healthy volunteers maximum 12.3+/-2.1%, P<0.001 compared with baseline; ARB-treated CHF patients maximum 9.3+/-3.3%, P<0.05 compared with baseline; P=not significant for difference between groups), but the increase in unstressed volume in ACEI-treated CHF patients was higher (maximum 28.8+/-7.8%, P<0.001 compared with baseline; P<0.05 for the difference between groups). In contrast, while the increase in blood flow in healthy volunteers (maximum 362+/-9%, P<0.001) and in ACEI-treated CHF patients (maximum 376+/-12%, P<0.001) was similar (P=not significant for the difference between groups), the increase in ARB-treated CHF patients was less (maximum 335+/-7%, P<0.001; P<0.05 for the difference between groups). Infusion of each receptor antagonist alone similarly reduced basal unstressed volume and blood flow in ACEI-treated CHF patients, but not in healthy volunteers or ARB-treated CHF patients. In conclusion, bradykinin does not contribute to basal venous tone in health, but in ACEI-treated chronic heart failure it does. In ARB-treated heart failure, venous responses to bradykinin are preserved but arterial responses are reduced compared with healthy controls. Bradykinin-mediated vascular responses in both health and heart failure are mediated by the B2, rather than the B1, receptor.
在本研究中，我们调查了基础状态下及动脉内输注缓激肽对健康志愿者（n = 20）、接受血管紧张素转换酶（ACE）抑制剂治疗的慢性心力衰竭患者（n = 16）以及接受血管紧张素受体阻滞剂（ARB）治疗的慢性心力衰竭患者（n = 14）的无应激前臂血管容量（静脉张力的一种测量指标）和血流量的影响。我们使用放射性核素体积描记法来研究缓激肽以及缓激肽拮抗剂B9340（1型/2型受体拮抗剂）和HOE140（2型拮抗剂）的作用。在健康志愿者和接受ARB治疗的慢性心力衰竭患者中，输注缓激肽以相似的剂量依赖性方式增加了无应激前臂血管容量（健康志愿者最大增加12.3±2.1%，与基线相比P<0.001；接受ARB治疗的慢性心力衰竭患者最大增加9.3±3.3%，与基线相比P<0.05；两组间差异无统计学意义），但接受ACE抑制剂治疗的慢性心力衰竭患者无应激容量的增加更高（最大增加28.8±7.8%，与基线相比P<0.001；两组间差异P<0.05）。相反，虽然健康志愿者（最大增加362±9%，P<0.001）和接受ACE抑制剂治疗的慢性心力衰竭患者（最大增加376±12%，P<0.001）的血流量增加相似（两组间差异无统计学意义），但接受ARB治疗的慢性心力衰竭患者的增加较少（最大增加335±7%，P<0.001；两组间差异P<0.05）。单独输注每种受体拮抗剂同样降低了接受ACE抑制剂治疗的慢性心力衰竭患者的基础无应激容量和血流量，但对健康志愿者或接受ARB治疗的慢性心力衰竭患者没有影响。总之，缓激肽对健康状态下的基础静脉张力没有作用，但在接受ACE抑制剂治疗的慢性心力衰竭中起作用。在接受ARB治疗的心力衰竭中，与健康对照相比，缓激肽的静脉反应得以保留，但动脉反应减弱。缓激肽介导的健康状态和心力衰竭中的血管反应均由2型受体而非1型受体介导。
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