The intrarenal generation of angiotensin II is required for experimental hypertension

Hypertension is a major risk factor for cardiovascular disease. While the cause of hypertension is multifactorial, renal dysregulation of salt and water excretion is a major factor. All components of the renin-angiotensin system are produced locally in the kidney, suggesting that intrarenal generation of angiotensin II plays a key role in blood pressure regulation. Here, we show that two mouse models lacking renal angiotensin converting enzyme (ACE) are protected against angiotensin II and l-NAME induced hypertension. In response to hypertensive stimuli, mice lacking renal ACE do not produce renal angiotensin II. These studies indicate that the intrarenal renin-angiotensin system works as an entity separate from systemic angiotensin II generation. Renal ACE appears necessary for experimental hypertension.