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Angiotensin II AT2receptor stimulation increases cerebrovascular resistance during hemorrhagic hypotension in rats

Authors
Journal
Regulatory Peptides
0167-0115
Publisher
Elsevier
Publication Date
Volume
52
Issue
1
Identifiers
DOI: 10.1016/0167-0115(94)90017-5
Keywords
  • Pd 123319
  • Losartan
  • Laser-Doppler Flowmetry
  • Cerebral Blood Flow
  • Sar1Ile8-Ang Ii
Disciplines
  • Medicine

Abstract

Abstract The effects of the angiotensin II (ANG II) AT 2 ligand PD 123319 and the AT 1 antagonist losartan on cerebral blood flow (CBF) were studied during hemorrhagic hypotension in anesthetized rats using laser-Doppler flowmetry. In the control group CBF remained stable when mean arterial blood pressure (MABP) was lowered from 84 mmHg (baseline) to 45 mmHg, whereafter there was a pressure dependent decrease in CBF indicating inadequacy of autoregulation. Cerebrovascular resistance (CVR) was reduced until MABP 40 mmHg, where a maximum dilation was reached. PD 123319 dose-dependently (3–30 mg/kg i.v.) increased CVR through all blood pressures. Losartan 3 mg/kg i.v. had an effect similar to PD 123319. Selective stimulation of AT 2 receptors with intravenous ANG II infusion, in the presence of AT 1 receptor blockade by losartan, also increased CVR. As a result, reduced CBF was seen in the treatment groups. The effects of ANG II and PD 123319 30 mg/kg were antagonized by the nonselective ANG II antagonist Sar 1,Ile 8-ANG II (4 μg/kg/min i.v.). None of the treatments affected baseline CBF. The results confirm that ANG II contributes to cerebrovascular resistance and participates in the regulation of CBF apparently through AT 2 receptors.

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