Renal kallikrein activity in spontaneously hypertensive rats

To assess possible roles of the renal kallikrein-kinin system in the development of spontaneous hypertension, we determined daily excretion of urinary total and active kallikrein in 6-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats for up to 2 weeks. We also evaluated the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, on the development of hypertension in the 6- week-old SHR on ordinary intakes of sodium or on sodium loading with 1% NaCl for up to 2 weeks. Active kallikrein was determined by its kininogenase activity, and the generated kinins were radio-immunologically measured. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin (200 μg/ml). Urinary active kallikrein excretion was significantly reduced in 7-week-old SHR (1.5 ± 0.2 μg/day compared to 2.8 ± 0.3 μg/day in WKY, P < 0.05) and in 8-week-old SHR (1.6 ± 0.2 μg/day compared to 3.2 ± 0.4 μg/day in WKY, P < 0.01). Urinary total kallikrein excretion was also reduced in the 7- and 8-week-old SHR whereas the ratio of active to total kallikrein did not change. In addition, renal contents of total and active kallikrein were significantly lower in the 8-week-old SHR than in the controls. Repeated daily subcutaneous administration of aprotinin (100 000 units/kg per day) for up to 2 weeks did not significantly affect the development of hypertension in the 7- and 8-week-old SHR on normal intakes of sodium or on sodium loading, although it significantly decreased urinary excretion and renal contents of active kallikrein under both sodium conditions. Thus the results of this study indicate that the renal kallikrein-kinin system may not play a major role in the development of hypertension in SHR. However, the pathophysiological relevance of the reduced renal kallikrein-kinin system to early development of spontaneous hypertension remains to be determined.