Nonpeptide angiotensin AT1 and AT2 receptor ligands modulate the upper limit of cerebral blood flow autoregulation in rats.

We investigated the effect of angiotensin AT1 and AT2 receptor blockade on the upper limit of CBF autoregulation in pentobarbital-anesthetized rats. CBF was measured by laser-Doppler flowmetry from the parietal cortex and MABP was increased by intravenous phenylephrine infusion. Neither the AT1 antagonist losartan nor the AT2 ligand PD 123319 nor angiotensin II (ANG II) in the presence of losartan affected baseline CBF. When the blood pressure was increased in the control group, CBF remained fairly constant up to 145 mm Hg and increased steeply after 150 mm Hg. Both PD 123319 (7-10 mg/kg) and losartan (1-10 mg/kg) shifted the upper limit of CBF autoregulation toward higher pressures. Intravenous infusion of PD 123319 was more effective than bolus injection. The losartan effect was dose dependent. Selective stimulation of AT2 receptors with an intravenous ANG II infusion (0.54 micrograms/min) in the presence of losartan did not reverse the effect of losartan on CBF autoregulation, but, on the contrary, appeared to further shift the upper limit of autoregulation toward higher pressures. The results implicate a role for both AT1 and AT2 angiotensin receptors in the regulation of CBF.