LONG-TERM INFUSION OF KALLIKREIN ATTENUATES RENAL INJURY IN DAHL SALT-SENSITIVE RATS

We investigated whether long-term infusion of kallikrein would attenua te renal injury in salt-induced hypertension in Dahl salt-sensitive (D ahl S) rats. A subdepressor dose of purified rat urinary kallikrein (R UK) (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 glome rular filtration rate was increased. These beneficial effects were ref lected morphologically by an attenuation of the glomerulosclerotic les ions and tubular injury seen in the hypertensive Dahl S rats. The kall ikrein infusion increased the urinary excretion of bradykinin and stim ulated the excretion of cyclic GMP, suggesting that the kallikrein-kin in-prostaglandin and nitric oxide axes were enhanced by the RUK infusi on. The alterations induced by such infusion were potentiated by the c oncomitant administration of the angiotensin converting enzyme inhibit or alacepril. These studies indicated that long-term replacement with rat tissue kallikrein attenuates renal injury in hypertensive Dahl S r ats, and this is probably mediated by an enhanced function of the kall ikrein-kinin-prostaglandin and nitric oxide systems. (C) 1997 American Journal of Hypertension, Ltd.