Role of AT1 and AT2 receptors in the plasma clearance of angiotensin II.
This study assessed the role of angiotensin (Ang) AT1 and AT2 receptors as modulators of the plasma clearance of Ang II. Groups of male spontaneously hypertensive rats (SHRs; n = 25) were given an intravenous injection of either saline, losartan, PD123319, losartan in combination with PD123319, or Sar1-Thr8-Ang II. One hour later, Ang II (0.5 microg/kg) was infused for 15 min into a vein. Immediately thereafter, 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 rats pretreated with either saline or PD123319 but not in those receiving losartan, losartan combined with PD123319, or Sar1-Thr8-Ang II. The plasma clearance of Ang II was significantly greater in rats injected with either PD123319, losartan combined with PD123319, or Sar1-Thr8-Ang II compared to those injected either saline or losartan. Furthermore, the half-life of Ang II in rats pretreated with saline or losartan was significantly greater than that measured in the other three groups. These results suggest that plasma clearance of Ang II in the SHRs is independent of an AT1 receptor, but plasma levels of the peptide are unexpectedly protected by an AT2 receptor-dependent mechanism.
Iyer
S N
SN
The Hypertension Center, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 21715, USA.
Chappell
M C
MC
Brosnihan
K B
KB
Ferrario
C M
CM
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006207:Half-Life; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; C014805:angiotensin II, Sar(1)-Thr(8)-; D019808:Losartan