[Renin-angiotensin-aldosterone system: an old system offering new drug targets for the cerebral circulation]

In a rat model of human essential hypertension (SHR), the chronic increase in cerebral arteriolar blood pressure is accompanied by remodelling with wall hypertrophy and a fall in diameter. The latter produces an increase in cerebrovascular resistance which maintains cerebral blood flow autoregulation at high systemic blood pressure levels, but accentuates hypoperfusion at low arterial pressures such as those observed during and following cerebral ischemia. Using ACE inhibitors and AT1 blockers we have shown that the normalisation of wall thickness is pressure-dependent but that the normalisation of arteriolar diameter relates to a pressure-independent mechanism involving aldosterone. This raises the possibility of new drug targets for arteriolar remodelling involving intracellular sodium-dependent modulation of protein metabolism.