Long-Term Infusion of Kallikrein Attenuates Renal Injury in Dahl Salt-Sensitive Rats

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• 作者：Yoshio Uehara ; Nobuhito Hirawa ; Atsushi Numabe ; Yukari Kawabata ; Toshio Ikeda ; Tomoko Gomi ; Atsuo Gotoh ; Masao Omata
• 关键词：Kallikrein ; Dahl salt-sensitive rats ; renal injury ; angiotensin converting enzyme inhibitor ; glomerulosclerosis ; arterial injury ; prostaglandin ; kinin
• 刊名：American Journal of Hypertension
• 出版年：1997
• 出版时间：May 1997
• 年：1997
• 卷：10
• 期：5, Supplement 1
• 页码：83S-88S
• 全文大小：456 K

文摘

We investigated whether long-term infusion of kallikrein would attenuate renal injury in salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. A subdepressor dose of purified rat urinary kallikrein (RUK) (700 ng/day) was infused intravenously by an osmotic minipump for 4 weeks in male Dahl S rats fed a high-salt (2 % NaCl) diet. This dose did not affect the time-dependent elevation of blood pressure. However, urinary protein excretion was significantly decreased, and the glomerular filtration rate was increased. These beneficial effects were reflected morphologically by an attenuation of the glomerulosclerotic lesions and tubular injury seen in the hypertensive Dahl S rats. The kallikrein infusion increased the urinary excretion of bradykinin and stimulated the excretion of cyclic GMP, suggesting that the kallikrein-kinin-prostaglandin and nitric oxide axes were enhanced by the RUK infusion. The alterations induced by such infusion were potentiated by the concomitant administration of the angiotensin converting enzyme inhibitor alacepril. These studies indicated that long-term replacement with rat tissue kallikrein attenuates renal injury in hypertensive Dahl S rats, and this is probably mediated by an enhanced function of the kallikrein-kinin-prostaglandin and nitric oxide systems.