Urinary kallikrein excretion and sodium metabolism in hypertensive patients.

Abstract

Urinary kallikrein excretion was measured in 21 healthy subjects and 44 patients with various types of hypertension.The kallikrein activity was determined by the method of esterolytic assay. The excretion rates in normal subjects were 112.9•}11.1 (S.E.) EU/day.The kallikrein excretion was decreased in patients with essential hypertension, the mean estimated values were 75.2•}10.0 EU/day. In this disease, however, an enhancement of urinary kallikrein was observed after sodium depletion.An obvious increase in kallikrein excretion was found in the primary aldosteronism.In primary aldosteronism and renovascular hypertension, one of the secondary aldosteronisms, there was a good correlation between the urinary kallikrein output and the urinary sodium excretion. The present data indicate that the renal kallikrein-kinin system, one of the renal anti hypertensive factors, is suppressed in essential hypertension and is under the influence of mineralocorticoid levels. -kallikrein esterolytic assay; kallikreinkinin system;various types of hypertensionThe presence of kallikrein in human urine has been known since Frey's original studies (Frey 1926). Urinary kallikrein differ distinctly from the plasma kallikrein (Webster and Pierce 1963) but they are indistinguishable from kidney kallikrein in molecular dimensions, pH optima and inhibitors behaviour (Nustad 1970). It is supposed that urinary kallikrein, produced in the kidney and excreted in urine, might be one of the renal antihypertensive factors. However, studies on the role of kallikrein-kinin system in hypertensive patients have hitherto been very scarce in the literature (Elliot and Nuzum 1934;Miwa 1965). Recently, Margolius and his coworkers (1971, 1972, 1974) described that abnormal excretion of kallikrein was observed in hypertensive patients. These reports attracted much attention of many researchers.In our laboratory, urinary kallikrein excretion was measured in various types of hypertension, and the influence of sodium depletion or sodium load on the urinary kallikrein output was studied in the essential hypertension patients to elucidate the pathophysiological significance of urinary kallikrein in hypertension.

Urinary prostaglandin and sodium metabolism in patients with essential hypertension.

“…Nasjletti and Colina Chourio (1976) showed that mineralocorticoids increased the urinary excretion of PGE-like substances in rat, and proposed the possibility that activation of the renal kallikrein-kinin system by aldosterone promoted renal release of PGE. Our previous data (Seino et al 1975 …”

Abnormal urinary kallikrein in hypertension is not related to aldosterone or plasma renin activity.

“…8 Urinary kallikrein was first reported to be subnormal in patients with essential hypertension in 1934 by Elliot and Nuzum 4 and more recently, several other groups reported similar findings. 5 …”

“…"-" Changes in sodium chloride balance are also associated with directionally similar changes in PRA, aldosterone, and urinary kallikrein 81 "• "• 2°-ss and the infusion of angiotensin into the renal artery produces an increase in urinary kallikrein. In view of the differences between our previous work" and others, 8 "* we wished to further study urinary kallikrein in subjects with essential hypertension and normals with a careful evaluation of the known factors which influence kallikrein. We particularly wished to further characterize the relationship of urinary kallikrein to renal function, PRA, aldosterone, and sodium and potassium balance.…”

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

“…Urinary and/or arterial TK can also be decreased in renovascular hypertension and genetically hypertensive rats (43,47,52,124). Although these reductions may be secondary to increases in blood pressure, decreased urinary kallikrein in (i) normotensive children of patients with essential hypertension, (ii) genetically hypertensive rats, and (iii) Dahl salt-sensitive rats that have not yet developed hypertension (48,108,159,257,278) suggests that the cause of the decrease may differ in each model.…”