Caveolin-1 Mediates Organ Damage

Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. High dietary sodium intake and genetic predisposition to salt sensitivity of blood pressure (BP) are of particular clinical relevance in Asian populations. Sacubitril/ valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, was hypothesized to increase natriuresis and diuresis and result in superior BP control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/ valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan treatment was associated with significant short-term increases in natriuresis and diuresis on day 1, without affecting serum electrolyte levels, and greater reductions in office BP, ambulatory BP (particularly, at nighttime despite of morning dosing), and N-terminal pro B-type natriuretic peptide levels (independent of office BP changes between treatments) on day 28. This is the first study to assess the pharmacodynamic effects of sacubitril/valsartan and valsartan in Asian patients with SSH. Further confirmatory studies are required to investigate if sacubitril/valsartan could constitute a novel therapeutic approach to standard of care therapy for patients with SSH. Caveolin-1 Mediates Organ Damage by Angiotensin II (p 79)