Impact of the renin-angiotensin system on cerebral perfusion following subarachnoid haemorrhage in the rat

1. This study investigated the effects of blocking the AT(1) angiotensin re ceptors with irbesartan, either peripherally or centrally, on systemic bloo d pressure, intracranial pressure and cerebral perfusion pressure following experimental subarachnoid haemorrhage (SAH) in urethane-anaesthetized rats . Sympathetic nervous activation was determined by measuring plasma noradre naline levels. 2. In untreated animals, SAH induced a sustained increased in intracranial pressure from 2.1 +/- 0.3 to 16 +/- 2 mmHg (3 h, P < 0.001). Cerebral perfu sion pressure was reduced by 20% (P < 0.001), this reduction being maintain ed for 3 h. Sympathetic activation was evident in the high level of plasma noradrenaline measured 3 h post-SAH (751 +/- 104 vs. 405 +/- 33 pg ml(-1), P < 0.05). 3. Acute peripheral pretreatment with irbesartan (3 mg kg(-1), I.V.) preven ted the rise in plasma noradrenaline and further aggravated the decrease in cerebral perfusion pressure by producing transient systemic hypotension (b lood pressure was 85 +/- 6 mmHg at 2 h post-SAH vs. 100 +/- 3 mmHg, P < 0.0 1). 4. Intracisternal pretreatment with irbesartan (0.035 mg) did not prevent t he rise in plasma noradrenaline post-SAH but enhanced the rise in intracran ial pressure by 75% compared with untreated animals. 5. This study demonstrates that peripheral endogenous angiotensin II intera cts with the sympathetic nervous system in order to maintain an adequate ce rebral perfusion following SAH. Endogenous angiotensin II in the brain seem s to exert a protective effect by counteracting the elevation in intracrani al pressure that occurs following experimental SAH.