Journal
HIGH ALTITUDE MEDICINE & BIOLOGY
Volume 2, Issue 3, Pages 349-360Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/15270290152608525
Keywords
atrial natriuretic peptide; HAPE; endotoxin; rats
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High altitude pulmonary edema (HAPE) is associated with increases in pulmonary arterial and hydrostatic pressures and an increase in pulmonary vascular permeability. There is evidence to suggest that inflammatory mediators may cause some forms of HAPE, and Salmonella enteritidis endotoxin (ETX) is known to activate neutrophils and inflammatory mediators, such as TNF-alpha and IL1-beta. Since HAPE has been produced in rats primed with ETX, we hypothesized that ANP release and action may ameliorate HAPE and that ANP blockade may exacerbate HAPE in ETX-primed rats exposed to high altitude (HA). Plasma ANP, right atrial ANP mRNA, and indexes of lung injury were measured in rats primed with endotoxin (ETX) (0.1 mg/kg BW, i.p.) and exposed to simulated HA (4267 m; P-B = 440 mmHg) for either 12 or 24 h. Catheters were chronically inserted into the right carotid artery, pulmonary artery, and jugular vein for assessment of hemodynamic parameters in response to ETX and/or HA. In addition, some rats were injected with an antibody against ANP (alpha ANP) prior to normoxic (NX) or HA exposure. Pulmonary arterial pressure increased in the alpha ANP group (50 +/- 20%; p less than or equal to0.05) and in the HA + alpha ANP (51 +/- 15%; p less than or equal to0.05) group at 12 h compared to NX sham rats injected with normal rabbit serum. In addition, systemic arterial pressure was significantly lower in the HA + ETX rats compared to HA + ETX + alpha ANP rats (p less than or equal to0.001). Plasma ANP levels were significantly higher at 12 and 24 h in ETX, HA, and HA + ETX groups (p less than or equal to0.05) compared to NX controls. There was an inverse relationship (p less than or equal to0.001) between plasma ANP levels and lung wet to dry (W/D) weight when data from NX, ETX, HA, and HA + ETX groups were pooled. The HA + alpha ANP rats had significantly higher lung W/D ratios (p<0.001) compared to sham rats. These results support the hypothesis that ANP, at physiological levels, modulates the development of pulnonary edema in HA-exposed ETX-primed rats.
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