Pretreatment renal vascular tone predicts the effect of specific renin inhibition on natriuresis in essential hypertension

Background In essential hypertension an elevated renal vascular resistance (RVR) may be a marker of renin-angiotensin-aldosterone system-mediated impa irment of renal sodium excretion. This hypothesis was tested by investigati ng whether, in subjects with essential hypertension, the natriuretic respon se to specific renin-angiotensin-aldosterone system (RAAS) blockade by reni n-inhibitor remikiren could be predicted from pretreatment renal vascular t one. 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 sodiu m excretion were studied under conditions of carefully controlled sodium ba lance. Results Pretreatment renal vascular tone showed considerable individual dif ferences: filtration fraction (FF) ranged from 21.2 to 30.3% and RVR from 1 8.8 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 c onsiderable interindividual variability in natriuretic response. During sin gle dose, cumulative sodium loss was 5.1 mmol per 5 h (-8.8 to +24.6), wher eas after 8 days treatment cumulative sodium loss was 72 +/- 30 mmol (-46 t o +187). The natriuretic response to remikiren during single as well as mul tiple 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.