ROLE OF AT(1) AND AT(2) RECEPTORS IN THE PLASMA-CLEARANCE OF ANGIOTENSIN-II

This study assessed the role of angiotensin (Ang) AT(1) and AT(2) rece ptors as modulators of the plasma clearance of Ang II. Groups of male spontaneously hypertensive rats (SHRs: n = 25) were given an intraveno us injection of either saline, losartan, PD123319, losartan in combina tion with PD123319, or Sar(1)-Thr(8)-Ang II. One hour later, Ang II (0 .5 mu g/kg) was infused for 15 min into a vein. Immediately there afte r, arterial blood samples were collected at regular intervals for the assay of plasma Ang II levels by radioimmunoassay. The infusion of Ang II significantly increased baseline mean arterial pressure (MAP) in r ats pretreated with either saline or PD123319 but not in those receivi ng losartan, losartan combined with PD 123319, or Sar(1)-Thr(8)-Ang II . The plasma clearance of Ang II was significantly greater in rats inj ected with either PD123319, losartan combined with PD 123319, or Sar(1 )- Thr(8)-Ang II compared to those injected either saline or losartan. Furthermore, the half-life of Ang II in rats pretreated with saline o r losartan was significantly greater than that measured in the other t hree groups. These results suggest that plasma clearance of Ang II in the SHRs is independent of an AT(1) receptor, but plasma levels of the peptide are unexpectedly protected by an AT(2) receptor-dependent mec hanism.