Human urinary and plasma kinins: relationship to sodium-retaining steroids and plasma renin activity.

Abstract

Sodium-retaining steroids increase urinary kallikrein but their effects on urinary kinins and plasma bradykinin are not known. Thirty-six normal subjects were studied during several different manipulations of dietary sodium and potassium or the administration of fludrocortisone or adrenocorticotropic hormone (ACTH). Urinary kallikrein and aldosterone excretion changed pari passu over a 30-fold range for kallikrein and an 80-fold range for aldosterone. Urinary kinin excretion was invariant. Plasma, bradykinin, on the other hand, responded to the same stimuli as plasma renin activity and not primarily to the level of sodium-retaining steroid. These studies show that: (1) urinary kallikrein is dependent on the level of aldosterone over a wide range of excretion values; (2) urinary kallikrein determines neither the level of urinary kinins nor the level of plasma kinins; (3) urinary kinins are independent of the level of sodium-retaining steroid; and (4) there is a strong correlation between plasma bradykinin and renin activity but not between plasma bradykinin and sodium-retaining steroid activty. We suggest that: (1) urinary kallikrein is an index of sodium-retaining steroid activity and may participate in the antinatriuretic and kaliuretic effects of these hormones; (2) plasma bradykinin is highly correlated with plasma renin activity because both responded to changes in extracellular fluid volume and not because angiotensin-converting enzyme controls both systems in an interrelated fashion; and (3) plasma bradykinin may act physiologically to antagonize angiotensin II and may contribute to maintenance of normal blood pressure in hyperreninemic states. Ore Res 44: [228][229][230][231][232][233][234][235][236][237]1979

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

“…Although other studies have indicated a parallelism between changes of plasma bradykininl and those of plasma angiotensin II or renin activity in response to changes of' posture, salt depletion, or saline infusioni in normal subjects (12,17), in the present study, treatmlent of' normal subjects with indomethacin decreased PRA but did not affect plasma bradykinin (Table I). This difference in the response of' plasma bradykinin in normal subjects and in patients with Bartter's syndrome may be attrib)uted to the mtuch higher basal valtues of plasma bradykiniin and( PRA in the patients with Bartter's syndromiie (Fig.…”

“…Urinary kallikrein exeretioni is inereased in conditions in which soditum-retaining steroids are presenit in excess (14)(15)(16)(17). Consistent with this observation are the report by Lechi et al (45) and otir presenit findings that patients with Bartter's syndrome excrete more kallikreini than normiial subjects.…”

“…The response of plasma bradykinin to postural change, sodium depletion, and saline infusion parallels temporally the response of PRA and of angiotensin II (12). Urinary kallikrein, which is derived from the kidney (13), is increased in conditions in which sodiumretaining steroids are present in excess (14)(15)(16)(17), but neither plasma nor urinary kinins are affected by sodium-retaining steroids (17).…”

The effect of converting enzyme inhibition with SQ20,881 on plasma and urinary kinins, prostaglandin E, and angiotensin II in hypertensive man.

“…17 Thus, because of its many actions, SQ20,881 is not simply a selective inhibitor of the renin-angiotensin system as is the antagonist and partial agonist, [Sar 1 , Ala']-angiotensin II. The latter had no significant depressor effect in normal-renin hypertensives, 18 but SQ20,881 significantly decreased diastolic pressure in more than 90% of normal-renin hypertensives. 17 Because of the proposed multiple actions of converting enzyme inhibition we investigated the extent to which changes in levels of kinins and prostaglandins, as well as angiotensin II, might contribute to the depressor effects of SQ20.881 in patients with normal and low-renin hypertension.…”

Amiloride inhibits mammalian renal kallikrein and a kallikrein-like enzyme from toad bladder and skin.

“…Dr. Chao is a Research Career Development Awardee of the National Heart, Lung, and Blood Instittite. Receivedfor publication 24 September 1979 and in revised fori 15 February 1980. ing effects upon sodium and water transport across membranes (1,2). In humans and rats, sodium-retaining steroids or maneuvers which increase aldosterone activity, such as reduced dietary sodium or increased dietary potassium increase renal and urinary kallikrein activity; whereas spironolactone reduces it (3)(4)(5)(6)(7)(8)(9). Kallikrein excretion is elevated in primary aldosteronism or Bartter's syndrome (10)(11)(12)(13).…”