Brain angiotensin: pathways and pharmacology

The existence of a brain renin-angiotensin system (RAS) as one of various tissue RASs is now firmly established. Angiotensin-containing pathways within brain areas involved in central blood pressure regulation have been described. Evidence from biochemical, neurophysiologic, pharmacologic, and most recently, molecular genetic studies indicate that the brain RAS is regulated independently of the hormonal RAS and may contribute to blood pressure control and body fluid homeostasis. In addition, circulating angiotensin II can exert some of its action through stimulation of brain angiotensin receptors accessible from the blood. In experimental animal preparations of hypertension, especially in spontaneously hypertensive rats, an overactive brain RAS may be one of the factors involved in pathogenesis and maintenance of hypertension. In spontaneously hypertensive rats, inhibitors of the angiotensin II-generating converting enzyme (CE) have been shown to lower blood pressure by a central action when applied to the brain and to inhibit brain CE when applied systemically. The pathogenetic mechanisms underlying a particular cardiovascular disease and the characteristics of the CE inhibitor used (e.g., its lipid solubility governing penetration into tissue) may determine the degree to which CE inhibition within a given organ, such as the brain, contributes to the action of these drugs.