DECREASED TOTAL AND ACTIVE URINARY KALLIKREIN IN NORMOTENSIVE DAHL SALT SUSCEPTIBLE RATS

Abnormalities in the kallikrein-kinin system have been found in human and animal models of essential hypertension. The purpose of this study is to assess the kallikrein-kinin system in normotensive Dahl salt sensitive (S) and salt resistant (R) rats on a zero sodium diet. Urinary kallikrein was measured at 7 and 12 wk of age by different techniques. When kallikrein activity was assessed, by a kininogenase assay, S rats excreted 66% (P < 0.001) and 75% (P < 0.01) as much kallikrein as R rats at 7 and 12 wk of age. Using an artificial substrate method (Kabi S-2266), S rats excreted 30% (P < 0.001) and 56% (P < 0.05) as much kallikrein as R rats at 7 and 12 weeks, respectively. Using a technique to measure total kallikrein, S rats excreted 53% (P < 0.001) and 65% (P < 0.05) as much kallikrein as R rats at 7 and 12 wk of age. Normotensive S rats failed to increase maximally kallikrein activity or total kallikrein when the diet was switched from a 0.4% to a .0064% sodium chloride diet. There was no difference in inhibitors, as measured by the recovery of purified kallikrein added to S and R urine (56 .+-. 21% vs. 53 .+-. 13%). Km values for S and R urinary kallikrein were similar (3.1 .+-. .5 .times. 105 vs. 2.6 .+-. .5 .times. 10-5 M/liter). Trypsin-activatable kallikrein was equivalent in the S and R rats on the .0064% and .4% sodium chloride diet. This study supports the hypothesis that there is diminished kallikrein activity in S rats, and that this is due to decreased kallikrein excretion rather than inhibitors in the urine, an abnormality in the enzyme or an inactive enzyme.