The renin-angiotensin system: a possible new target for depression

Abstract

Depression remains a debilitating condition with an uncertain aetiology. Recently, attention has been given to the renin-angiotensin system. In the central nervous system, angiotensin II may be important in multiple pathways related to neurodevelopment and regulation of the stress response. Studies of drugs targeting the renin-angiotensin system have yielded promising results. Here, we review the potential beneficial effects of angiotensin blockers in depression and their mechanisms of action. Drugs blocking the angiotensin system have efficacy in several animal models of depression. While no randomised clinical trials were found, case reports and observational studies showed that angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had positive effects on depression, whereas other antihypertensive agents did not. Drugs targeting the renin-angiotensin system act on inflammatory pathways implicated in depression. Both preclinical and clinical data suggest that these drugs possess antidepressant properties. In light of these results, angiotensin system-blocking agents offer new horizons in mood disorder treatment.

Keywords: ATR1; ATR2; Angiotensin; Angiotensin receptor blockers; Angiotensin-converting enzyme inhibitors; Depression; Inflammation; Mas; Psychiatry; Renin–angiotensin system.

Fig. 1

Pathways involved in neuronal damage of angiotensin II through AT1 receptor agonism. Ang II, angiotensin II; AT1R, angiotensin II receptor type 1; PGE2, prostaglandin E2; Cox-2, Cyclooxygenase-2; PPAR-γ, peroxisome proliferator-activated receptor gamma; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; iNOS, inducible nitric oxide synthase; NO, nitric oxide; ROS, reactive oxygen species

Fig. 2

Pathway from angiotensinogen to AT1, AT2 and Mas receptors. ACE, Angiotensin-converting enzyme