Habituation to repeated stress is reversed by systemic angiotensin II: a mechanism involving nitric oxide in the paraventricular nucleus of the hypothalamus

Abstract

Long‐term angiotensin II (Ang) induced hypertension leads to activation of hypothalamic neurons. In the present study, we determined whether this treatment might prevent the habituation to repeated stress (RS, 60 min airjet daily for 7 days). Rabbits were exposed to RS alone or combined with Ang (6 weeks, 20ng/kg/min) or neither (control). RS exposure reduced the renal sympathetic nerve activity (RSNA) response to acute stress and inhibited neuronal activation (Fos expression) in the hypothalamus. Ang treatment restored the RSNA response to acute stress and also increased the activation of the paraventricular nucleus (PVN, 16±3 vs 39±3, P<0.001) compared with RS, but not of the amygdala, dorsomedial hypothalamus, arcuate and supraoptic nuclei. The activated PVN neurons contained NADPH oxidase (11±3 v 18±5 P<0.01) and nitric oxide (NO) synthase (16±3 vs 45±4, P<0.001) but not vasopressin or corticotrophin releasing factor. Thus, superoxide and NO production in the PVN is associated with elevated sympathetic responses to RS exposure in Ang‐induced hypertensive rabbits. This study was supported by the National Health & Medical Research Council of Australia.