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Pretreatment renal vascular tone predicts the effect of specific renin inhibition on natriuresis in essential hypertension
Author(s) -
Pieter van Paassen,
GJ Navis,
PE de Jong,
Dick de Zeeuw
Publication year - 1999
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1999.00573.x
Subject(s) - natriuresis , endocrinology , medicine , renin–angiotensin system , aldosterone , effective renal plasma flow , filtration fraction , plasma renin activity , essential hypertension , vascular resistance , renal function , blood pressure , angiotensin ii , kidney , renal blood flow
Background In essential hypertension an elevated renal vascular resistance (RVR) may be a marker of renin‐angiotensin‐aldosterone system‐mediated impairment of renal sodium excretion. This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific renin‐angiotensin‐aldosterone system (RAAS) blockade by renin‐inhibitor remikiren could be predicted from pretreatment renal vascular tone. Materials and methods Renal hemodynamics, and the effects of single ( n = 17) and multiple doses ( n = 8, 8 days) of remikiren (600 mg day −1 ) on sodium excretion were studied under conditions of carefully controlled sodium balance. Results Pretreatment renal vascular tone showed considerable individual differences: filtration fraction (FF) ranged from 21.2 to 30.3% and RVR from 18.8 to 33.5 10 −2 mmHg min mL −1 in the single dose study, and FF from 20.8 to 24.9% and RVR from 14.8 to 28.8 10 −2 mmHg min mL −1 in the multiple dose study. Remikiren induced a fall in blood pressure, FF and RVR, with considerable interindividual variability in natriuretic response. During single dose, cumulative sodium loss was 5.1 mmol per 5 h (−8.8 to +24.6), whereas after 8 days treatment cumulative sodium loss was 72 ± 30 mmol (−46 to +187). The natriuretic response to remikiren during single as well as multiple dose significantly correlated with pretreatment renal vascular tone (estimated from FF and RVR) but not with remikiren‐induced changes in renal hemodynamics or in hormonal parameters. Cumulative sodium loss was largest in patients with a higher pretreatment FF and RVR ( r = 0.74, P < 0.001 and r = 0.52, P < 0.05, respectively, single dose; and r = 0.75, P < 0.05 and r = 0.73, P < 0.05, respectively, multiple dose). Conclusion These data support the hypothesis that in essential hypertension an elevated renal vascular tone is a marker of RAAS‐mediated impairment of sodium excretion.