Campbell D J, Duncan A M, Kladis A, Harrap S B
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
J Hypertens. 1995 Jul;13(7):739-46.
To determine whether tissue kinin levels in spontaneously hypertensive rats (SHR) differ from those in normotensive rats.
The tissue levels of bradykinin-(1-9) and its metabolites bradykinin-(1-7) and bradykinin-(1-8) were measured in kidney, and bradykinin-(1-9) and bradykinin-(1-7) were measured in adrenal, lung, heart, aorta, brown adipose tissue and brain of male SHR and the normotensive genetically homogeneous Donryu rat strain, at age 6, 10 and 20 weeks.
In comparison with Donryu rats, bradykinin-(1-7), bradykinin-(1-8) and bradykinin-(1-9) levels were increased in kidney, and bradykinin-(1-7) and bradykinin-(1-9) levels were increased in adrenal, lung and heart of SHR aged 6 weeks. Bradykinin-(1-7) levels remained elevated in adrenal and lung of SHR aged 10 weeks. The bradykinin-(1-7): bradykinin-(1-9) ratio for kidneys of SHR was reduced at all ages and the bradykinin-(1-8):bradykinin-(1-9) ratio was reduced at age 10 and 20 weeks. Bradykinin peptide levels in aorta, brown adipose tissue and brain were similar for SHR and Donryu rats.
The increased levels of bradykinin-(1-9) and its metabolites in kidney, adrenal, lung and heart tissues of young SHR suggest increased kallikrein activity in these tissues. Moreover, the reduced bradykinin-(1-7):bradykinin-(1-9) and bradykinin-(1-8):bradykinin-(1-9) ratios in kidneys of SHR indicate reduced endopeptidase- and carboxypeptidase-mediated metabolism of bradykinin-(1-9), which may have contributed to the increased bradykinin-(1-9) levels in this tissue. Together with the previously reported hypotensive effect of bradykinin-(1-9) antagonism in young SHR, and the cosegregation of the SHR kallikrein gene with blood pressure, the increased bradykinin-(1-9) levels in tissues of young SHR are consistent with a role for this peptide in the pathogenesis of hypertension in those rats.
确定自发性高血压大鼠（SHR）的组织激肽水平是否与正常血压大鼠不同。
测量了6周龄、10周龄和20周龄雄性SHR以及血压正常的基因纯合的东京大鼠品系的肾脏中缓激肽-（1-9）及其代谢产物缓激肽-（1-7）和缓激肽-（1-8）的组织水平，以及肾上腺、肺、心脏、主动脉、棕色脂肪组织和大脑中缓激肽-（1-9）和缓激肽-（1-7）的水平。
与东京大鼠相比，6周龄SHR的肾脏中缓激肽-（1-7）、缓激肽-（1-8）和缓激肽-（1-9）水平升高，肾上腺、肺和心脏中的缓激肽-（1-7）和缓激肽-（1-9）水平升高。10周龄SHR的肾上腺和肺中缓激肽-（1-7）水平仍然升高。SHR肾脏中缓激肽-（1-7）：缓激肽-（1-9）的比值在所有年龄段均降低，缓激肽-（1-8）：缓激肽-（1-9）的比值在10周龄和20周龄时降低。SHR和东京大鼠主动脉、棕色脂肪组织和大脑中的缓激肽肽水平相似。
年轻SHR的肾脏、肾上腺、肺和心脏组织中缓激肽-（1-9）及其代谢产物水平升高表明这些组织中激肽释放酶活性增加。此外，SHR肾脏中缓激肽-（1-7）：缓激肽-（1-9）和缓激肽-（1-8）：缓激肽-（1-9）的比值降低表明缓激肽-（1-9）的内肽酶和羧肽酶介导的代谢减少，这可能导致了该组织中缓激肽-（1-9）水平的升高。结合先前报道的缓激肽-（1-9）拮抗剂对年轻SHR的降压作用，以及SHR激肽释放酶基因与血压的共分离，年轻SHR组织中缓激肽-（1-9）水平的升高与该肽在这些大鼠高血压发病机制中的作用一致。
