Plasma and tissue kallikrein–kinin systems during acute administration of frusemide in normotensive and hypertensive humans

Abstract

1. This study aims to further elucidate the role of the tissue and plasma kallikrein-kinin systems in blood pressure, electrolyte and volume homoeostasis. Components thereof and of the renin-angiotensin-aldosterone system were measured in conjunction with frusemide administration, in normotensive subjects and in patients with primary hypertension. 2. Frusemide increased plasma pre-kallikrein, angiotensin II and aldosterone concentrations and plasma renin activity, whereas the plasma level of tissue kallikrein remained unchanged. Basal values and the induced changes were similar in both groups. 3. Frusemide increased the urine volume and the excretion of Na+, K+, Mg2+, Cl-, aldosterone, prostaglandin E2 and tissue kallikrein. These changes were similar in both groups, but the total tissue kallikrein excretion was significantly lower in the hypertensive patients. Excretion of electrolytes and hormones was also measured during three 24 h urine collection periods and did not differ between the two groups. 4. Thus, acute administration of frusemide to hypertensive patients and normal subjects increased the plasma level of pre-kallikrein, possibly indicating less activation to kallikrein and subsequently less kinin generation in the blood stream. This also suggests a role for the plasma kallikrein-kinin system in the regulation of vascular tone and blood volume. Circulating tissue kallikrein does not seem to be acutely involved. 5. Urinary excretion of kallikrein is reduced in patients with primary hypertension after the administration of frusemide, apparently without affecting the renal excretory response.

Insuficiencia cardíaca

“…In all patients, urinary hK1 amidase activity was reduced 19 . Ohman and Karlberg 20 observed that furosemide increases the urine volume and the excretion of tissue kallikrein in normotensive individuals and in patients with primary hypertension. Thus the diminished levels of hK1 amidase activity (instead of their expected increasing) in patients treated with furosemide, in our study, could be explained by their having HF 19 .…”

“…Some experimental studies were published since our publication, regarding ischaemic HF. Spillmann et al 20 aimed to test the original hypothesis that hK1 gene delivery to the peri-infarct myocardium would prevent post-ischemic HF. They induced MI in anesthetized mice by permanently occluding the left coronary artery.…”