Brain angiotensin- converting enzyme type 2 shedding contributes to the development of neurogenic hypertension

Huijing Xia, Srinivas sriramula, Kavaljit H. Chhabra, Eric Lazartigues.Circ Res.2013;113:1087-1096; doi:10.1161/circresaha.113.301811.

It has been shown that overactivity of the renin angiotensin system can lead to hypertension. Ace 2 is an enzyme that can convert angII to ang 1-7. Ang1-7 has an vasodilatory affect on vasculature.  Ace 2 is down regulated in hypertension further contributing to the dysfunction of the RAS. What is really interesting is that it has been shown that ectodomain of ACE2 is cleaved and can be found in CSF. Thus hypertension leads to ace 2 shedding. The question becomes what is responsible for the removal of ace 2 from the cell membrane. So the hypothesis was adam 17 is responsible for the cleavage of ace 2 and leading to the development of hypertension.  So they used transgenic mice in order to test there hypothesis. Using mice that had overexpression of Ace2 in neurons that were DOCA- high salt diet mice improved the spontaneous Baroreflex function. Ace2 overexpression also leads to decreased vasopressin release, norepinephrine, and ang II. Along with that vagal tone was restored and sympathetic drive to the heart and vasculature was brought back down to control levels. They knockdown adam 17 and showed that this prevented the development of hypertension and lead to a decrease in ace 2 shedding in the csf. These data demonstrate that hypertension that is due to a high salt diet may be leading to increased adam 17 expression and leading to decrease ace 2 expression on neurons and ultimately leading to hypertension. –MD