The renin system: Variations in man measured by radioimmunoassay or bioassay

Abstract

The renin system: Variations in man measured by radioimmunoassay or bioassay.Using a basic incubation procedure followed by either pressor bioassay or radioimmunoassay of angiotensin I, normal values for plasma renin activity (PRA) were defined in 52 normal subjects over the range of physiological variation which occurs in relation to changes in sodium balance.Complete interchangeability of results derived from the two different methods was achieved by the application of a correction factor based on the observed lower pressor activity of angiotensin I.Plasma renin activity exhibits a consistent dynamic relationship to the daily rate of urinary sodium excretion.The values ranged from 0.5 to 2.8 ng/ml/hr when sodium excretion was above 150 mEq/day, from 1.4 to 6.3 ng/ml/hr when sodium excretion was between 50 and 150 mEq/day, and up to 21 ng/ml/hr when sodium excretion was below 50 mEq/day.However, a more precise index derives from using limits inscribed by the whole curve as a nomogram.Plasma renin substrate measurements did not vary with changes in sodium balance.Its concentration measured by radioimmunoassay ranged from 900 to 2200 ng/ml but intra-individual variation was small.These values are considerably higher but closer to the true value than previously reported assays which erroneously compared angiotensin I generated during the incubation with the more pressor angiotensin II.Renin substrate reactivity, an arbitrary index derived from adding a fixed amount of purified human renin to plasma, also did not vary with changes in sodium balance but it did vary directly with the absolute substrate concentration.In normal subjects the mean reaction velocity was 59 × 10 3 ng/ml/hr/GU renin and this ranged from 35 to 89 ng/ml/hr/GU.These observations are in keeping with first order kinetics in which both enzyme and substrate concentrations are rate limiting.However, the study demonstrates that physiologically, changes in substrate concentration are not normally determinants of the rate of angiotensin generation since there was no relationship between substrate concentration and the endogenous level of plasma renin activity.Systemic arterio-venous differences in plasma renin were not observed.However, in 43 patients with benign essential hypertension, net and fairly equal secretion of renin by the two kidneys was demonstrated.Mean renal vein renin activity exceeded arterial levels by 0.48 ng/ml/hr when the mean arterial renin activity was 1.62 ng/ml/hr.