Ceranapril and cerebral blood flow autoregulation

To investigate the effect of the new angiotensin converting enzyme inhibitor ceranapril (1 mg/kg) on the cerebral blood flow (CBF) autoregulation in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).

Sixteen WKY rats and 16 SHR were given ceranapril 1 mg/ml intravenously and compared with two untreated control groups (n = 16). The rats were furthermore divided into subgroups of eight to study the upper and lower limits of autoregulation separately.

CBF was measured using the intracarotid xenon-133 injection technique. The arterial blood pressure was raised stepwise by noradrenaline or lowered stepwise by controlled bleeding, in order to study CBF over a range of mean arterial pressure (MAP) values.

Baseline MAP was significantly lower in the WKY rat group than in the SHR group. There was no significant difference in baseline CBF between the treated and the untreated groups. Following ceranapril administration, baseline MAP was reduced by 10 mmHg in WKY rats and by 20 mmHg in SHR, and the limits of CBF autoregulation were reset at lower blood pressure levels. In WKY rats as well as in SHR, ceranapril significantly reduced the lower blood pressure limit of CBF autoregulation. In both strains the upper limit of CBF autoregulation was reduced significantly.

Ceranapril preserves CBF autoregulation and significantly shifts the limits of CBF autoregulation towards lower blood pressure values.