A hypothesis regarding the function of angiotensin peptides in the brain.
Studies of the in vivo and in vitro metabolism of angiotensin peptide precursors, and of angiotensin II (Ang II) in tissues, has revealed the possibility that some of the fragments formed through specific enzymatic pathways are bioactive. There is evidence that Ang III is as potent as Ang II in stimulating thirst and causing aldosterone secretion. New findings from this laboratory have led us to reevaluate the concept that fragments of angiotensins derived from the amino (N-) terminus are devoid of biological activity. Using in vitro and in vivo techniques, we showed that Ang-(1-7) is processed from Ang I in amounts equal to or greater than Ang II. In addition, Ang-(1-7) generation is not dependent upon Ang I converting enzyme (ACE) activity in homogenates of canine brain stem. This heptapeptide promotes release of vasopressin from perifused hypothalamo-neurohypophysial explant and stimulates neural responses when microinjected into the vagal-solitary complex. The data supporting these findings are discussed below.
Ferrario
C M
CM
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195-5070.
Santos
R A
RA
Brosnihan
K B
KB
Block
C H
CH
Schiavone
M T
MT
Khosla
M C
MC
Greene
L J
LJ
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001923:Brain Chemistry; D004285:Dogs; D010446:Peptide Fragments / Q000502:physiology; D013894:Thirst / Q000502:physiology
D010446:Peptide Fragments; D000804:Angiotensin II