ANGIOTENSIN-II RECEPTOR ANTAGONIST CV-11974 AND CEREBRAL BLOOD-FLOW AUTOREGULATION

Objective: To investigate whether the angiotensin II (Ang II) subtype 1 receptor (AT(1)) antagonist CV-11974 had a similar effect to angiote nsin converting enzyme inhibitors on cerebral blood flow autoregulatio n in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensi ve rats (SHR). Methods: Sixteen WKY rats and 16 SHR were given CV-1197 4 0.1 mg/kg intravenously and compared with two control groups (n=16). Their cerebral blood flow was measured with the intracarotid xenon-13 3 injection method and blood pressure was raised by noradrenaline infu sion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of -squares analysis. Results: The dose of CV-11974 given lowered blood p ressure but did not influence baseline cerebral blood flow. In WKY rat s the lower limit of autoregulation in control rats was 60+/-3 mmHg, w hereas after CV-11974 administration it was 48+/-2 mmHg (P<0.01). In S HR the corresponding values were 85+/-2 and 78+/-2 mmHg, respectively (P<0.05). In WKY rats the upper limit of autoregulation in control rat s was 144+/-5 mmHg, whereas after CV-11974 administration it was 126+/ -7 mmHg (P<0.05). In SHR the corresponding figures were 174+/-8 and 14 4+/-6 mmHg, respectively (P<0.01). Conclusion: Thus, the AT(1) recepto r antagonist, although it did not influence baseline cerebral blood fl ow, shifted the autoregulation curve towards lower blood pressure. Thi s effect is similar to that of angiotensin converting enzyme inhibitor s, and might be due to release of Ang II-dependent tone in the larger cerebral resistance vessels.