Abstract 233: Evidence for an Interaction Between Systemic and Renal Angiotensinogen in the Control of Arterial Pressure

Abstract

Both the liver and proximal tubule make angiotensinogen (AGT), and overexpression of AGT in either region increases blood pressure (BP). To determine the relative contributions of renal and systemic AGT in modulating BP, mice were used with AGT overexpression in kidney (K), liver (L) or both sites (KL). Male transgenic and wildtype (WT) controls aged 24 weeks underwent BP recording via telemetry and metabolic cage studies on normal (0.25%) and high (3.2%) sodium diets. Mean BP (MAP) was higher in K and KL vs L and WT mice fed normal salt, while MAP in L mice was higher than controls. High salt intake did not alter MAP in WT, K or KL mice but increased it in L mice. Plasma AGT levels, plasma renin concentration, urine Na excretion and urine volume were similar between groups regardless of sodium intake. Urinary AGT (ng/day) on normal sodium intake was: WT: 5±1, L: 4±1, K: 20±5 and KL: 34±9. High salt increased urine AGT in all groups (WT: 19±4, L: 42±8, K: 290±75, KL: 407± 72). High salt did not alter plasma AGT levels but reduced plasma renin concentration in all groups. Taken together, these data show a correlation between urinary AGT and BP. Mice with renal AGT overexpression may be maximally hypertensive on a normal sodium diet since renal AGT is already high. Mice with liver AGT overexpression have mild hypertension on a normal sodium diet that is exacerbated by high sodium intake; this is associated with a significant increase in urinary AGT as compared to WT animals. Thus, systemic AGT may have the potential to regulate renal AGT and this effect may be a key determinant of BP.