Inhibiting renin-angiotensin in the brain: the possible therapeutic implications

The renin-angiotensin system (RAS) within the brain is involved in central blood pressure regulation. Biochemical and neurophysiological studies sugge st that the brain system is regulated independently of the peripheral RAS a nd that the system may also contribute to blood pressure control and body f luid homeostasis. In addition, circulating angiotensin II can exert some of its actions through the stimulation of angiotensin subtype 1 (AT(1)) and s ubtype 2 (AT(2)) receptors within the brain. As in peripheral tissues, the AT(1) receptor mediates the central actions of angiotensin II on osmotic co ntrol and blood pressure regulation. The AT(2) receptor appears to be invol ved in brain development and neuronal regeneration, but may also modulate s ome effects of central AT(1) receptor stimulation. Selective non-peptide an tagonists of the AT(1) receptor have been shown to inhibit not only periphe ral, but also central AT(t) receptors after systemic application. In animal models, treatment with AT(1) receptor antagonists proved to be beneficial with respect to stroke incidence and outcome. Other animal studies have sho wn that the AT(1) receptor antagonists enable endogenous angiotensin II to stimulate nerve generation via AT(2) receptors.