The kallikrein-kinin system in primary hypertension : dynamics of circulating components of the kallikrein-kinin system in relation to the renin-angiotensin-aldosterone system

Sammanfattning: Kinins are potent vasodilatory and blood pressure lowering peptides, with additional effects on renal handling of electrolytes and water. The kallikrein-kinin system consists of two separate entities, one confined to the circulation and the other to both tissues and the circulation. The role of the plasma system and the circulating part of the tissue system in circulatory homeostasis and electrolyte and metabolism is unclear, as well as the pathogenetic involvement of these systems in primary hypertension.The aims of the studies were to investigate the possible participation of the plasma kallikrein~ kinin system and the circulating components of the tissue kallikrein-kinin system in the regulation of blood pressure, electrolyte and water balance; possible differences between normotensive and primary hypertensive subjects with respect to these systems; relations between the kallikrein-kinin systems and the renin angiotensin-aldosterone system; evidence of regulated release of prorenin and the possible participation of the kallikrein-kinin systems in the conversion of prorenin to renin.Twentyseven patients with primary hypertension and 16 normotensive control subjects were given furosemide 80 mg p.a. in the first study. In the following 3 studies 15 hypertensive and 15 normotensive subjects participated. Graded i.v. infusion of angiotensin 11 during 3h, i.v. infusion of 2000ml 0.9% sodium chloride during 4h, and fludrocortisone 0.2 mg o.d. p.a. during 7 days were administered in separate protocol.1. Plasma prekallikrein levels did not differ between normotensive and hypertensive subjects. Furosemide increased plasma prekallikrein, angiotensin II had no effect and sodium chloride infusion and fludrocortisone administration reduced plasma prekallikrein. 2. Tissue kallikrein in plasma did not change during these experiments. 3. There were minute differences between normotensive and hypertensive subjects in the activation of both the plasma and the tissue kallikrein-systems and in their relation to blood pressure levels and renal sodium and water handling. 4. Alterations of prorenin levels in plasma evoked by changes in blood pressure, angiotensin II levels, electrolyte and water balance were parallel with those of renin and without any signs of separate specific regulatory mechanisms. 5. There were no signs that the plasma or circulating tissue kallikrein-kinin system participated in the conversion of prorenin to renin. 6. There were no clear functional relations between endogenous mineralocorticoids and circulating tissue kalikrein or plasma prekallikrein.In conclusion: The data demonstrate alterations in the activity of the plasma kallikrein-kinin system, related to electrolyte and volume balance; differences between normotensive and hypertensive subjects, the pathophysiological relevance of which remains to be elucidated; minor differences in the reactivity of circulating tissue kallikrein in hypertensive subjects, but no obvious participation of the circulating components of the tissue system. Hypertensives have higer renin/prorenin ratio there are no signs of specific regulation of prorenin release or participation of circulating kallikreins in the conversion of prorenin to renin. Some of these differences may have relevance to the abnormal blood pressure levels in patients with primary hypertension.