Abstract 2520: Unprecedented Renal Responses to Direct Blockade of the Renin-Angiotensin-System with Aliskiren, a Novel Renin Inhibitor
Background: Direct renin inhibitors hold real promise in providing optimal blockade of the renin-angiotensin system. As a measure of that blockade, we have examined renal plasma flow (RPF) responses in a standardized protocol. We predicted that the potent oral renin inhibitor aliskiren would produce renal vascular responses exceeding those induced by other renin system blockers.
Methods: We studied 20 healthy normotensives (15M, 5F) on a 10 mmol Na+ diet. Subjects received two or three escalating doses of aliskiren (75, 150, 300 or 600 mg) on separate study days, or placebo. RPF was measured by clearance of para-aminohippurate.
Results: Aliskiren induced dose-related renal vasodilation substantially larger than previously seen with other agents (Fig⇓). Responses to 75 mg were similar to those induced by ACEI (rise in RPF 93 ±20 ml/min/1.73m2 ); to 150 mg, similar to ARBs ( 124 ±13 ml/min/1.73m2). Rise in RPF was maximal at the 600 mg dose, reaching unprecedented vasodilation (197 ± 27 ml/min/1.73m2). In serial studies there was significant residual vasodilation 48 hours after each dose (P<0.01). We found a significant natriureses. Urinary sodium on entry was <4 ± 0 mmol/24 hours; it rose to 30 ± 11 after 75 mg and peaked at 35 ± 9 mmol/24 hours after the 150 mg dose (P<0.01).
Conclusion: Renal vasodilation in healthy people with the potent renin inhibitor aliskiren far exceeded responses seen with ACEI and ARBs. The effects were longer-lasting, and associated with significant natriuresis. These results indicate that aliskiren may provide more complete and thus more effective blockade of the renin system, perhaps reflecting blockade of prorenin.