Urinary Kallikrein Excretion in Essential and Mineralocorticoid Hypertension

Abstract

A B S T R A C T Urinary kallikrein excretion has been reported to be decreased in patients with essential hypertension and elevated in patients with primary aldosteronism as a reflection of mineralocorticoid activity. Low renin essential hypertension (LREH) has been postulated to result from excess production of an unknown mineralocorticoid(s ,ug/24 h for black normals) and a failure to achieve metabolic balance in 11/13 patients. Thus, the lesser kallikrein stimulation appeared to result from these two factors. Black and white hypertensives with creatinine clearance <80 ml/min had little increase in urinary kallikrein excretion with Florinef or low sodium diet.5 of 12 patients with primary aldosteronism or 17a-hydroxylase deficiency did not have an elevated urinary kallikrein excretion rate. Mild renal insufficiency may have contributed to this finding in two of these five patients. Nevertheless, this finding illustrates a limitation to the use of urinary kallikrein excretion rate as an index of mineralocorticoid activity. However, it appears that the majority of patients with LREH have no evidence for excess production of an unknown mineralocorticoid. The failure to find a decrease in urinary kallikrein excretion in racially matched patients with essential hypertension and normal renal function questions the postulate of a role of the kallikrein-kinin system in the initiation of essential hypertension.

Enhanced Blood Pressure Sensitivity to Deoxycorticosterone in Mice With Disruption of Bradykinin B 2 Receptor Gene

“…20 The seminal finding that the renal KKS, a potent natriuretic and vasodilator system, is typically activated in human hypermineralocorticosteroidism as well as in rats given longterm DOC has been interpreted as a compensatory response to counteract the vasopressor and sodium-retaining effects of mineralocorticoids. [11][12][13] Consistent with the results obtained in other species is the finding that urinary kinins are increased in DOC-treated mice. The mechanism by which mineralocorticoids stimulate the renal KKS is not yet clear.…”

“…Interestingly, at variance with other models of genetic or experimental hypertension characterized by a defective renal synthesis and excretion of kallikrein, 6 -10 clinical forms of primary aldosteronism as well as experimental hypertension induced by DOC show an activated KKS. [11][12][13] The possibility that this alteration represents a compensatory response to counteract the development of hypertension induced by DOC is based mainly on pharmacological studies in rats, 14,15 showing that the hypertensive effect of mineralocorticoid administration is enhanced by the concomitant blockade of B 2 receptors with icatibant, a longacting analogue antagonist of bradykinin. 16,17 Unfortunately, receptor antagonists are not devoid of unspecificity.…”

Sodium susceptibility and potassium effects in young patients with borderline hypertension.

“…'4 18 In addition, black hypertensive subjects have a deficiency of the kallikrein-kinin renal vasodilatory and natriuretic system. 39 We measured urinary kallikrein in the present study, but there was no significant difference in urinary kallikrein in the young patients with borderline hypertension and the normotensive subjects. The sympathetic nervous system40 and the renin-angiotensin system4' have important influences over renal sodium excretion.…”

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.…”