Central angiotensin and baroreceptor control of circulation

Angiotensin (Ang) receptors are located in many important central nuclei involved in the regulation of the cardiovascular system. While most interest has focused on forebrain circumventricular actions, areas of the brainstem such as the nucleus of the solitary tract and the ventrolateral medulla contain high concentrations of AT1 receptors. The present review encompasses the physiological role of Ang II in the hindbrain, particularly in relation to its influence on baroreflex control mechanisms. In rabbits there are sympatho-excitatory AT1 receptors in the rostral ventrolateral medulla (RVLM), accessible to Ang II from the cerebrospinal fluid. Activation of these receptors acutely increases renal sympathetic nerve activity (RSNA) and RSNA baroreflex responses. However, blockade of endogenous Ang receptors in the brainstem also shows sympathoexcitation, suggesting there is greater endogenous activity of a sympathoinhibitory Ang II action. Microinjections of angiotensin antagonists into the RVLM showed relatively little tonic activity of endogenous Ang II influencing sympathetic activity in conscious rabbits. However, Ang II receptors in the RVLM mediate sympathetic responses to airjet stress in conscious rabbits. Similarly with respect to heart rate baroreflexes, there appears to be little tonic effect of angiotensin in the brainstem in normal conscious animals. Chronic infusion of Ang II for two weeks into the fourth ventricle of conscious rabbits inhibits the cardiac baroreflex while infusion of losartan increases the gain of the reflex. These actions suggest that Ang II in the brainstem modulates sympathetic responses depending on specific afferent and synaptic inputs in both the short term but importantly also in the long term, thus forming an important mechanism for increasing the range of adaptive response patterns.