Dopamine-angiotensin interactions in the basal ganglia and their relevance for Parkinson's disease

Abstract

Renin-angiotensin systems are known to act in many tissues, for example, the blood vessel wall or kidney, where a close interaction between angiotensin and dopamine has been demonstrated. Regulatory interactions between the dopaminergic and renin-angiotensin systems have recently been described in the substantia nigra and striatum. In animal models, dopamine depletion induces compensatory overactivation of the local renin-angiotensin system, which primes microglial responses and neuron vulnerability by activating NADPH-oxidase. Hyperactivation of the local renin-angiotensin system exacerbates the inflammatory microglial response, oxidative stress, and dopaminergic degeneration, all of which are inhibited by angiotensin receptor blockers and inhibitors of angiotensin-converting enzymes. In this review we provide evidence suggesting that the renin-angiotensin system may play an important role in dopamine's mediated neuroinflammation and oxidative stress changes in Parkinson's disease. We suggest that manipulating brain angiotensin may constitute an effective neuroprotective strategy for Parkinson's disease.

Keywords: Parkinson's; aging; angiotensin; degenerative disease; dopamine; neurodegeneration; neuroinflammation; oxidative stress; renin-angiotensin system.