Basal and potassium-evoked release of angiotensin II from the rat hypothalamus

Although the protein components of the renin-angiotensin system have been localized in the brain, it remains to be established whether or not angiotensin II (Ang II) is generated locally and secreted into the interstitial fluid of the brain. We have addressed this issue in vitro by perifusing explants of the rat hypothalamo-neurohypophysial system (HNS) (5 explants per chamber, 37 degrees C) with Krebs solution at a rate of 1 ml/min. The release of Ang II immunoreactivity (Ang II-ir) and arginine vasopressin immunoreactivity (AVP-ir) in the medium was measured 3-5 h after HNS dissection and again after addition of potassium (K+) to the perifusate. Samples of the fluid perifusing the HNS were collected for 30-min intervals and concentrated using Sep-Pak C18 cartridges. Release of Ang II-ir was significantly increased during perifusion with 70 mM K+ (from 29 +/- 14 pg/30 min to 80 +/- 17 pg/30 min, P less than 0.01). This increase coincided with a dramatic rise in the release of AVP-ir (from 50 +/- 35 pg/30 min to values above 2000 pg/30 min). The associated release of Ang II-ir in response to depolarization by K+ is consistent with the hypothesis that Ang II can be secreted by neuronal elements of the brain, possibly via a regulated pathway.