Cerebroventricular and Intravascular Metabolism of [125I]Angiotensins in Rat

This study compared the metabolism of 125I]angiotensin II (AII), 125I]angiotensin III (AIII), and 125I]Sar1,Ile8-AII (SI-AII) in the vascular and cerebroventricular compartments. Using HPLC methods to monitor degradation the following t1/2 values were established in the vascular compartment: AII, 12.7 +/- 1.4 s; AIII, 16.3 +/- 0.7 s; and SI-AII, 100.7 +/- 7.3 s. HPLC analysis also revealed that 125I]AII is converted in an obligatory manner to 125I]AIII during its degradation sequence. Cerebrospinal fluid contained no degradative capacity for 125I]AII but exhibited a significant capacity to degrade 125I]AIII. A technique that combined the intra-cerebroventricular injection of 125I]angiotensins followed by focused microwave fixation to stop all peptidase activity was used to determine the half-life of 125I]angiotensins in the ventricular space. Results indicated very rapid metabolism of angiotensins with the following t1/2 values: AII, 23.0 s; and AIII, 7.7 s. This extremely rapid, differential, and sequential metabolism of AII and AIII in two relevant body fluid compartments underscores the need for caution when interpreting data derived from intravascular and intracerebroventricular application of angiotensins. In addition the faster metabolism of AIII than AII in the ventricular space indicates that the actual potency of AIII at central angiotensin receptors is being underestimated.