The aims of this study were to determine whether ANG II is involved in the
central integration of the cardiac sympathetic afferent reflex (CSAR), and
if this central effect of ANG II is mediated by the AT(1) receptor. Experim
ents were undertaken in dogs that were anesthetized with alpha-chloralose,
sinoaortic denervated, and vagotomized. The renal sympathetic nerve activit
y (RSNA) responses to varying frequency and voltage stimulation of cardiac
sympathetic afferent nerves were used to evaluate the central sensitivity o
f the CSAR. In two groups of dogs, two doses (50 and 100 ng/min icv) of ANG
II were acutely infused. In a third group of dogs, ANG II was chronically
infused for 3 days (100 ng/min, 1 mu l/h icv). We found that acute infusion
into the cerebroventricle of two doses of ANG II did not affect the centra
l sensitivity of the CSAR or the baseline hemodynamics, but the baseline RS
NA increased significantly during the infusion of the higher dose of ANG II
. However, chronic intracerebroventricular infusion of ANG II enhanced the
central sensitivity of the CSAR significantly In addition, chronic intracer
ebrovetricular infusion of ANG II elicited a significant increase in water
intake and in arterial pressure from the first and second day of infusion,
respectively. In the group th at received chronic intracerebroventricular i
nfusion of ANG II, the administration of an AT(1)-receptor antagonist losar
tan (0.125 mg/kg icv) abolished ANG II-induced augmentation of the CSAR. Th
ese results suggest that chronic elevation of central ANG II can sensitize
the CSAR via central AT(1) receptors.