Circulating kallikreins during sodium chloride infusion in normal and hypertensive humans

The stimuli generating kinins participating in blood pressure, volume and sodium homeostasis and their origin are not fully known. We studied the effects of a combined sodium and volume load on circulating plasma and tissue kallikreins. Normal saline (2000 ml) was infused over 4 h in 14 subjects with primary hypertension and 15 age- and sex-matched normotensive control subjects. The infusion increased blood pressure slightly in both groups. Plasma prekallikrein levels fell in both groups (normotensives: 98 +/- 4 to 87 +/- 5%, p = 0.002; hypertensives: 106 +/- 5 to 94 +/- 6%, p = 0.003), but more rapidly in normotensives. Circulating tissue kallikrein did not change significantly in the normotensive group but was reduced in the hypertensive group. Sodium excretion during the infusion correlated negatively with changes in plasma prekallikrein and positively with plasma levels of tissue kallikrein in the normotensive group only. Urinary tissue kallikrein excretion during the infusion increased significantly only in the normotensive group. The levels or changes of circulating prekallikrein and tissue kallikrein were not related to the levels or changes in blood pressure in any of the groups. In the hypertensive group there was a negative correlation between blood pressure changes and urinary sodium and tissue kallikrein excretion. Thus, in normotensive subjects an acute sodium and volume load appears to activate the plasma kallikrein system and the activation correlates with sodium excretion. There are subtle differences in subjects with primary hypertension. The relevance of these differences with respect to the pathogenesis of primary hypertension remains to be evaluated.