Role of kallikrein-kinin system and sodium metabolism in the development of hypertension in spontaneously hypertensive rats

In the present study, two protocols were used to assess possible role of renal kallikrein-kinin system and sodium balance in the development of hypertension in young spontaneously hypertensive rats (SHR). In the first protocol, daily excretion of urinary kallikrein and systolic blood pressure were measured in the 5-week-old SHRs on regular diet or on sodium loading with 10% NaCl solution for drinking water for up to 3 weeks. In the second protocol, chronic effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, on the development of hypertension was studied in young SHRs on regular diet or on sodium loading with 1% NaCl. Subcutaneous injection of aprotinin (100,000 units/kg/day) or vehicle as controls was continued every 12 hours for up to 2 weeks. Daily systolic blood pressure in the rats was monitored by an indirect tail cuff method. Kallikrein was determined by its kininogenase activity, and the generated kinins were radioimmunologically measured. Urinary kallikrein excretion and renal kallikrein content were significantly increased in SHRs on sodium loading compared to those in SHRs on regular diet. However, chronic sodium loading with 1% NaCl did not affect the progressive development of hypertension in young SHRs. Aprotinin did not affect the development of hypertension in young SHRs on regular diet or on sodium loading, although aprotinin decreased significantly urinary excretion of kallikrein and renal kallikrein content on both conditions. Therefore present results indicate that reduced renal kallikrein-kinin system may not be involved in the development of hypertension in young SHRs on regular diet and on sodium loading. Additionally, it is reconfirmed that sodium is not a main determinant of the progressive development of hypertension in young SHRs.