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No effect of angiotensin II AT2-receptor antagonist PD 123319 on cerebral blood flow autoregulation

Neurobiology Research Unit, Rigshospitalet

Olaf B Paulson

Neurobiology Research Unit, Rigshospitalet, paulson{at}nru.dk

Svend Strandgaard

Department of Nephrology, Herlev Hospital, Copenhagen University Hospitals, Denmark

Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT₁-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT₂-receptors in the regulation of the cerebral circulation is uncertain. Hence, the present study investigated the effect on CBF autoregulation of blocking of angiotensin AT₂-receptors with PD 123319 in spontaneously hypertensive rats (SHR). Anaesthetised and ventilated SHR were given PD 123319, 0.36 mg/kg/min, intravenously, and compared with a control group. CBF was measured by the intracarotid ^133-xenon injection method and BP was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis. PD 123319 did not influence baseline CBF, but resulted in a minor BP decrease (10 control and 10 treated rats). The lower limit of CBF autoregulation (eight treated and eight control) as well as the upper limit of CBF autoregulation (eight treated and eight control) were not significantly different in PD 123319 and control animals (lower limit treated 102±4 mmHg and control 94±4; NS, and upper limit treated 171±10 mmHg and control 162±7; NS). These findings indicate that acute AT₂-receptor blockade does not influence CBF autoregulation.

Key Words: angiotensin II • angiotensin II receptor antagonist • autoregulation • cerebral blood flow • PD 123319 • hypertension

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 3, 188-192 (2001)
DOI: 10.3317/jraas.2001.026


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