Effect of angiotensin-related antihypertensives on brain neurotransmitter levels in rats

Abstract

The extensive clinical experience of angiotensin converting enzyme inhibitors and angiotensin AT 1 receptor antagonists as antihypertensive agents provide numerous examples of anecdotal evidence of improvements in cognition and mood. This study aimed to determine the effect of chronic treatment with the angiotensin converting enzyme inhibitor, perindopril, and the angiotensin AT 1 receptor antagonist, candesartan, on central neurotransmitter levels in the rat. Perindopril (1.0 mg/kg/day) or candesartan (10 mg/kg/day) was administered via the drinking water at for 1 week, while controls received water alone. At the end of treatment rats were sacrificed, brains removed and discrete regions dissected and analysed for noradrenaline, dopamine and its major metabolites, and serotonin content. As shown previously we found an increase in striatal dopamine levels after perindopril treatment, though this did not extend to the mesolimbic system with neurotransmitter levels unchanged in the hippocampus, nucleus accumbens and frontal cortex. Conversely, candesartan administration produced no change in dopamine, but significant decreases in both DOPAC and HVA in the striatum. In addition chronic candesartan infusion produced a significant increase in the levels of hippocampal noradrenaline and serotonin; and frontal cortex serotonin content. These results demonstrate that while angiotensin converting enzyme inhibitors and angiotensin AT 1 receptor antagonists act as antihypertensives by affecting the renin–angiotensin system, they have divergent actions on brain neurochemistry.