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 suggest that the brain system is regulated independently of the peripheral RAS and that the system may also contribute to blood pressure control and body fluid homeostasis. In addition, circulating angiotensin II can exert some of its actions through the stimulation of angiotensin subtype 1 (AT1) and subtype 2 (AT2) receptors within the brain. As in peripheral tissues, the AT1 receptor mediates the central actions of angiotensin II on osmotic control and blood pressure regulation. The AT2 receptor appears to be involved in brain development and neuronal regeneration, but may also modulate some effects of central AT1 receptor stimulation. Selective non-peptide antagonists of the AT1 receptor have been shown to inhibit not only peripheral, but also central AT1 receptors after systemic application. In animal models, treatment with AT1 receptor antagonists proved to be beneficial with respect to stroke incidence and outcome. Other animal studies have shown that the AT1 receptor antagonists enable endogenous angiotensin II to stimulate nerve generation via AT2 receptors.