Urine angiotensinogen and salt-sensitivity and potassium-sensitivity of blood pressure

Urinary excretion of angiotensinogen [urine angiotensinogen (UAGT)] has been proposed as a biomarker of intrarenal renin-angiotensin system activity. We investigated the association between UAGT and salt-sensitivity and potassium-sensitivity of blood pressure (BP) among Genetic Epidemiology Network of Salt Sensitivity study participants.

The intervention consisted of a 7-day low-sodium diet (51.3  mmol sodium/day), 7-day high-sodium diet (307.8  mmol sodium/day), and 7-day high-sodium diet with potassium supplementation (307.8  mmol sodium/day and 60  mmol potassium/day). Twenty-four-hour UAGT was estimated at baseline and at the end of each intervention for 100 randomly selected participants.

Median UAGT (μg/24  h) and UAGT-to-creatinine ratio (UAGT/Cr, μg/g) were significantly reduced during the low-sodium and potassium-supplementation interventions and increased during the high-sodium intervention (both P = 0.01). Baseline log-transformed UAGT and UAGT/Cr ratio were significantly positively associated with BP at baseline and at the end of each intervention. For example, one standard deviation higher log-UAGT/Cr ratio (1.2  μg/g) was associated with a 5.0-mmHg (95% confidence interval 2.3-7.8) higher SBP at the end of the high-sodium intervention, after adjusting for multiple covariates (P = 0.003). In addition, one standard deviation higher log-UAGT/Cr ratio was associated with a 1.6-mmHg increase in age-adjusted and sex-adjusted SBP from the low-sodium intervention to the high-sodium intervention (95% confidence interval 0.1-3.1, P = 0.04). This association was no longer statistically significant after multivariable adjustment.

These data indicate that elevated UAGT are associated with BP sodium sensitivity. Augmentation of intrarenal renin-angiotensin system activity may play an important role in developing salt-sensitive hypertension.