Abstract
Central sympathetic activation is one of the mechanisms of salt-sensitive hypertension and reactive oxygen species (ROS) has been proposed to play a key role in it. We examined whether adrenomedullin (AM), an antioxidant peptide, might contribute to the central regulation of arterial pressure (AP). Four groups of mice were used: AM-knockout mice (AM(+/-)) and wild-type littermates (AM(+/+)), which were fed with normal or high salt diet. In urethane-anesthetized mice, intracerebroventricular infusion of NaCl increased AP and sympathetic nerve activity (SNA) in a dose-dependent fashion. The elevation of AP and SNA in salt-loaded AM(+/-) was significantly greater than those in the other three groups (p<0.05). In freely moving mice, similar exaggerated hypertension was observed in salt-loaded AM(+/-). Pretreatment with a membrane-permeable superoxide dismutase mimetic, Tempol, completely blocked the responses in both AP and SNA, indicating participation of ROS. NaCl-induced ROS production in the hypothalamus was significantly greater in salt-loaded AM(+/-) than in AM(+/+), as determined by chemiluminescence assay. AM contents in the brain from AM(+/+) mice were significantly elevated by salt loading, whereas they were not elevated in AM(+/-) mice. These results suggest that AM in the brain inhibits sympathetic activation in salt-induced hypertension through its antioxidant effect. [Jpn J Physiol 54 Suppl:S99 (2004)]
