Angiotensinogen (AGT) is synthesized in the liver and proximal tubule. AGT overexpression at either site might increase blood pressure (BP). We used transgenic mice with AGT overexpression in proximal tubule (K), liver (L), or both sites (KL) to determine the relative contributions of hepatic- and proximal tubule–derived AGT in modulating BP.Methods
Hepatic AGT overexpression was obtained using the albumin enhancer promoter; the kidney androgen protein gene was used for proximal tubule AGT overexpression. BP and renin angiotensin system parameters were examined in male KL, K, L, and wild-type mice on normal and high-sodium diets.Results
Compared with wild-type mice, K and KL mice had higher BP on normal and high-sodium diets. L mice had similar BP to wild-type mice on a normal-sodium diet, but high sodium intake caused hypertension. There were no differences in plasma AGT, plasma renin concentration, urine volume, or urine sodium excretion between the groups. Urine AGT and angiotensin II (Ang II) excretion were higher in KL and K mice than in L or wild-type mice on a normal-sodium diet and increased with high sodium intake. During high sodium intake, urine AGT and Ang II were higher in all transgenic mice vs wild-type mice.Conclusions
Mice with liver AGT overexpression manifest salt-sensitive hypertension, whereas mice with renal AGT overexpression are hypertensive regardless of salt intake. Systemic AGT may stimulate endogenous renal AGT synthesis during high sodium intake, leading to hypertension in L mice. This suggests that systemic and renal AGT may interact to modulate BP.