Angiotensin II AT2 receptor stimulation extends the upper limit of cerebral blood flow autoregulation: agonist effects of CGP 42112 and PD 123319.
The effects of the angiotensin II AT2 receptor ligands CGP 42112 and PD 123319, the AT1 antagonist losartan, and the nonselective angiotensin II antagonist Sar1,Ile8-angiotensin II on the upper limit of CBF autoregulation were studied in pentobarbital-anesthetized rats. Blood pressure was increased by intravenous phenylephrine infusion, while CBF was measured continuously from the parietal cortex by laser-Doppler flowmetry. Intravenous infusions of CGP 42112 (0.1 and 1 mg kg-1 min-1) and PD 123319 (0.36 and 1 mg kg-1 min-1) shifted the upper limit of CBF autoregulation toward higher blood pressures without affecting baseline CBF. Sar1,Ile8-angiotensin II (4 micrograms kg-1 min-1) had no effect on baseline CBF or CBF autoregulation but antagonized the effect of CGP 42112 and PD 123319. Losartan (10 mg/kg i.v. bolus) reduced baseline blood pressure and CBF and shifted the autoregulation curve toward higher blood pressures. Sar1,Ile8-angiotensin II blocked the effect of losartan on baseline CBF but not on CBF autoregulation. These results suggest that both CGP 42112 and PD 123319 exert their effects on CBF autoregulation through stimulation of angiotensin II AT2 receptors. The mechanism by which losartan affects CBF remains unclear.
Näveri
L
L
Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
Strömberg
C
C
Saavedra
J M
JM
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007275:Injections, Intravenous; D019808:Losartan; D008297:Male; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C060894:CGP 42112A; C073402:PD 123319; D010656:Phenylephrine; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D019808:Losartan