Urinary kallikrein and plasma renin activity as determinants of renal blood flow. The influence of race and dietary sodium intake.

Abstract

A B S T R A C T We investigated the relationship of the kallikrein-kinin system and the renin-angiotensin system in the regulation of blood pressure, salt and water excretion, and renal blood flow. Normotensive and hypertensive black and white men were studied during unrestricted sodium intake as well as on a 10-meq/day sodium intake; potassium intake was held constant throughout the study (80 meq/day).During unrestricted sodium intake, urinary kallikrein activity was greater in white normotensives than white hypertensives or black normotensives. There was no difference (P > 0.05) between white and black hypertensives or between black normotensives and black hypertensives. All groups had greater urinary kallikrein activity on low sodium vs. unrestricted sodium intake, but the increase in black hypertensives was small, and they excreted significantly less kallikrein than the other groups on the low sodium diet. Plasma renin activity showed similar increments after sodium restriction in all groups. Urinary kallikrein activity correlated with renal blood flow in all groups except the black normotensives on low sodium intake. Renal blood flow could be correlated uniformly with log (urinary kallikrein activity/supine plasma renin activity) in all groups on either diet. Urinary sodium and potassium excretion and urine volume were not different among the groups. We concluide: (a) support the concept that the kallikrein-kinin system and the renin-angiotensin system contribute to the regulation of renal blood flow and may account for racial differences in renal vascular resistance. INTRODUCTIONKallikrein is an enzyme that catalyzes the formation of the vasodilator hormones, lysyl-bradykinin (kallidin) and bradykinin, from a plasma alpha-2 globulin substrate, kininogen (1). Urinary kallikrein appears to be derived from the kidney and differs from the enzyme that circulates in plasma (2). It has been proposed that kallikrein exists in the renal cortex and may occupy a location that is juxtaposed to the enzyme renin (3). Although a physiologic function for lysyl-bradykinin, the enzymatic product, has not been established, pharmacologic infusion studies have shown that the peptide is a natriuretic and vasodilatory compound (4).A number of studies in humans and experimental animals have attempted to determine the relationship between urinary kallikrein activity and blood pressure regulation (5-9). Although most investigators feel that kallikreins could influence blood pressure, the meaning of these findings is controversial. Based on provocative preliminary observations (10) and the aforementioned studies, it seemed appropriate to examine the simultaneous influence of race and blood pressture on urinary kallikrein activity. In addition, we have examined the association between kallikrein in uirine and factors that have been related to blood pressure regulation including urinary volume, soditum excretion, plasma renin activity, and renal blood flow. These latter studies were designed to determine a possible physiologic role ...

Why is plasma renin activity lower in populations of African origin?

“…Moreover, low PRA has also been found in blacks on diets where the intake of sodium has been carefully controlled and lower PRA has been found on both low and high sodium intakes. 6,12 By contrast, several studies 9,13,46,47 have reported a lower urinary potassium excretion in blacks. And although this has not been confirmed in every comparative study, 36,48 a lower potassium intake could be important as changes in potassium intake, though to a smaller extent, can also influence renin release largely through the impact on sodium balance.…”

“…However, 'low renin hypertension' is clearly an arbitrary definition and the actual frequency in blacks has ranged widely depending on the cut-off value taken to delimit the state of 'low PRA'. Furthermore, suppressed PRA is also present in both normotensive and hypertensive blacks even when on a low salt diet 6,12 and in response to loss of sodium as induced by administration of diuretics. 23,24 The low PRA in blacks is also associated with a lower plasma angiotensin II independent of ACE activity.…”

“…17 Interestingly, slightly lower PRA has also been reported in black neonates. 20 While a lower PRA was originally defined in relation to hypertension in blacks, lower PRA has also been found in normotensives 6,8,9,11,13 suggesting that the lower PRA is not simply a consequence of the high blood pressure, at least in individuals without malignant hypertension and renal failure. That the lower PRA is a characteristic feature of blacks as a group is also supported by a lack of difference in PRA between normotensive and hypertensive blacks from rural African regions.…”

Renal kallikrein excretion: role of ethnicity, gender, environment, and genetic risk of hypertension

“…In particular, we studied three ethnic groups from widely differing geographic sites of ancestry (Europe, sub-Saharan Africa, and east Asia), since previous reports on kallikrein excretion have not directly compared more than two such groups. 1,8,9,11,20 Reports over the past two decades have demonstrated substantial ethnic differences in renal kallikrein excretion, 2,6-9 with African-Americans displaying consistently lower kallikrein activity than Caucasians. Here we found a substantial diminution in urinary kallikrein excretion in African-Americans (Table 1; F = 5.3, P = 0.006), but no difference (P = 1.0) between Caucasian and Asian values.…”

“…Finally, previous carefully controlled studies, with fixed and comparable dietary exposures, have clearly documented ethnicity as a determinant of kallikrein excretion, especially in studies comparing African-Americans and Caucasians. 11,20 How (mechanistically) might potassium have influenced the ethnic variations in kallikrein excretion in our sample? One likely mediator is aldosterone, since potassium directly stimulates aldosterone biosynthesis and release from the adrenal cortex zona glomerulosa 8,34 and kallikrein is an aldosterone responsive target in man.…”