No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation

T M Estrup1, O B Paulson, S Strandgaard

  • 1Neurobiology Research Unit, Rigshospitalet, Copenhagen, Denmark.

Insights

Blocking angiotensin AT2-receptors with PD 123319 did not alter cerebral blood flow (CBF) autoregulation limits in spontaneously hypertensive rats. This suggests AT2-receptors do not play a significant role in regulating CBF autoregulation acutely.

Area of Science:

  • Neuroscience
  • Cardiovascular Physiology
  • Pharmacology

Background:

  • The renin-angiotensin system influences cerebral blood flow (CBF) autoregulation.
  • Angiotensin-converting enzyme inhibitors and AT1-receptor antagonists affect CBF autoregulation limits.
  • The specific role of AT2-receptors in cerebral circulation regulation remains unclear.

Purpose of the Study:

  • To investigate the effect of blocking angiotensin AT2-receptors on cerebral blood flow (CBF) autoregulation.
  • To determine if AT2-receptor blockade influences the limits of CBF autoregulation in spontaneously hypertensive rats (SHR).

Main Methods:

  • Administration of PD 123319 (an AT2-receptor antagonist) to anesthetized, ventilated spontaneously hypertensive rats (SHR).
  • Measurement of cerebral blood flow (CBF) using the intracarotid 133xenon injection method.
  • Determination of autoregulation limits by altering blood pressure (BP) via noradrenaline infusion and controlled hemorrhage, followed by least-sum-of-squares analysis.

Main Results:

  • PD 123319 did not affect baseline CBF but caused a minor decrease in blood pressure.
  • No significant differences were observed in the lower or upper limits of CBF autoregulation between PD 123319-treated rats and control animals.
  • The lower limit of autoregulation was 102±4 mmHg (treated) vs. 94±4 mmHg (control), and the upper limit was 171±10 mmHg (treated) vs. 162±7 mmHg (control).

Conclusions:

  • Acute blockade of angiotensin AT2-receptors does not significantly influence the autoregulation of cerebral blood flow in spontaneously hypertensive rats.
  • These findings suggest that AT2-receptors may not play a critical role in the acute regulation of cerebral circulation under these experimental conditions.

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