INCREASED LEVELS OF BRADYKININ AND ITS METABOLITES IN TISSUES OF YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

Objective: To determine whether tissue kinin levels in spontaneously hypertensive rats (SHR) differ from those in normotensive rats. Design and methods: 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. Results: 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. Conclusion: 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.