Response of the renal kallikrein-kinin system, intravascular volume, and renal hemodynamics to sodium restriction and diuretic treatment in essential hypertension.

Abstract

The renal kallikrein-kinin system, distinct from the plasma system, is an enzyme sequence producing kinins, principally lysyl bradykinin. While the functions of the system have not been conclusively established, it has been implicated in renal vasodilation and natriuresis, although the evidence is often conflicting. Measurement of urinary kallikrein excretion is the most common way to assess the system, although kallikrein excretion and kinin excretion are often dissociated. Kallikrein excretion is influenced by several hormonal systems, as well as dietary alterations, disease states (including hypertension), and numerous drugs. Kallikrein excretion is diminished in hypertension (especially hypertension with reduced renal function), suggesting involvement in the pathogenesis of the disease. Dietary sodium restriction increases kallikrein excretion while lowering blood pressure, but the blood pressure reduction correlates with plasma volume contraction rather than the increase in kallikrein. Thiazide diuretics lower blood pressure and renal vascular resistance while increasing kallikrein excretion, and blood pressure "responders" to thiazides have a greater kallikrein increment than the "nonresponders," suggesting a role for renal kallikrein in the hypotensive response to thiazides.