Renin-angiotensin system: biochemistry and mechanisms of action.

Circulation: Overall Regulation

The renin-angiotensin system plays an important role in the regulation of arterial blood pressure and in the development of some forms of clinical and experimental hypertension. It is an important blood pressure control system in its own right but also interacts extensively with other blood pressure control systems, including the sympathetic nervous system and the baroreceptor reflexes. Angiotensin (ANG) II exerts several actions on the sympathetic nervous system. These include a central action to increase sympathetic outflow, stimulatory effects on sympathetic ganglia and the adrenal medulla, and actions at sympathetic nerve endings that serve to facilitate sympathetic neurotransmission. ANG II also interacts with baroreceptor reflexes. For example, it acts centrally to modulate the baroreflex control of heart rate, and this accounts for its ability to increase blood pressure without causing a reflex bradycardia. The physiological significance of these actions of ANG II is not fully understood. Most evidence indicates that the actions of ANG to enhance sympathetic activity do not contribute significantly to the pressor response to exogenous ANG II. On the other hand, there is considerable evidence that the actions of endogenous ANG II on the sympathetic nervous system enhance the cardiovascular responses elicited by activation of the sympathetic nervous system.

Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure

• During recent years the nature of the considerable contribution of the sympathetic nervous system to renal hypertension has become somewhat more clear, due in part to the unexpected discoveries that angiotensin is not simply a direct vasoconstrictor agent but is almost ubiquitous in its actions. Among these actions are several on the sympathetic nervous system that appear to intensify its effects on the peripheral vascular system. It stimulates release of catechols from the adrenal medulla (1); at certain dose levels it facilitates ganglionic transmission (2); and it sensitizes the neurovascular effector so that the effects of sympathetic vasomotor discharge are augmented (3). This latter effect may depend in part on prevention of reuptake of released norepinephrine (4). For a long time it was considered unlikely that angiotensin had any effect on the central nervous system since theoretically it does not cross the blood-brain barrier. Then Bickerton and Buckley (5), in 1961, cross-perfused the head of a recipient dog, isolated from its own circulation and connected to the body only by the spinal cord, with blood from a donor animal. When angiotensin was injected into the circulation of the donor animal it raised the systemic arterial pressure in the recipient's trunk as well as in the donor animal. Because

Cardiovascular Effects of Angiotensin Mediated by the Central Nervous System

TIGERSTEDT and Bergman established a role for the kidney in blood-pressure regulation at the close of the 19th century. In a classic experiment, they produced hypertension in dogs by injecting a cr...

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Papers

The cardiovascular response to vertebral artery infusions of angiotensin in the dog.