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 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.


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).


CONCLUSIONS
These data support the hypothesis that in essential hypertension an elevated renal vascular tone is a marker of RAAS-mediated impairment of sodium excretion.
van Paassen
P
P
Department of Medicine, State University, Groningen, the Netherlands.
Navis
G J
GJ
De Jong
P E
PE
De Zeeuw
D
D
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D012083:Renin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D007093:Imidazoles; D012083:Renin; D012964:Sodium; D000092502:Renin Inhibitors; C065581:remikiren