Abnormalities in kallikrein excretion in spontaneously hypertensive rats

Abstract

Experiments were conducted to examine kallikrein excretion in 12-wk-old anesthetized and conscious Okamoto-Aoki spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Urinary excretion of active and total kallikrein was determined at spontaneous pressures and in response to acute decreases in renal perfusion pressure (RPP; suprarenal aortic constriction). Under basal conditions, active kallikrein excretion was lower in SHR compared with WKY whether conscious (4.4 +/- 1.7 vs. 9.4 +/- 1.3 pkat . min-1 . g kidney wt-1) or anesthetized (5.7 +/- 1.3 vs. 10.4 +/- 1.7). In both anesthetized SHR and WKY, excretion of active and total kallikrein was directly related to RPP after 20 mmHg decrements in RPP and was depressed in SHR at each pressure level. The slope of the relation between active kallikrein excretion and pressure was less in SHR (0.06 +/- 0.01 vs. 0.14 +/- 0.05 pkat . min-1 . g kidney wt-1 . mmHg-1). Thus kallikrein excretion is set at a lower level in SHR and is less responsive to changes in RPP. These strain differences are not related to urine flow, Na excretion, or glomerular filtration rate (GFR) since the values were the same in both strains at each pressure level. Analysis of covariance indicated a significant correlation between active kallikrein excretion and RPP in WKY and SHR, with RPP accounting for 92% of the variation in the kallikrein data. GFR, Na excretion, and urine flow rate were not significantly correlated to active kallikrein and were responsible for only 2% of the variation.(ABSTRACT TRUNCATED AT 250 WORDS)