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Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294
We tested the hypotheses that
hypoxic exposure is associated with exacerbated pulmonary hypertension
and right ventricular (RV) enlargement, reduced atrial natriuretic
peptide (ANP) clearance receptor (NPR-C) expression, and enhanced
B-type natriuretic peptide (BNP) expression in the absence of
ANP. Male wild-type [ANP(+/+)], heterozygous [ANP(+/
)], and
homozygous [ANP(/)] mice were studied after a 5-wk hypoxic
exposure (10% O2). Hypoxia increased RV ANP mRNA and
plasma ANP levels only in ANP(+/+) and ANP(+/) mice. Hypoxia-induced
increases in RV pressure were significantly greater in ANP(/) than
in ANP(+/+) or ANP(+/) mice (104 ± 17 vs. 45 ± 10 and
63 ± 7%, respectively) as were increases in RV mass (38 ± 4 vs. 26 ± 5 and 29 ± 4%, respectively). NPR-C mRNA levels
were greatly reduced in the kidney, lung, and brain by hypoxia in all three genotypes. RV BNP mRNA and lung and kidney cGMP levels were increased in hypoxic mice. These findings indicate that disrupted ANP
expression worsens hypoxic pulmonary hypertension and RV enlargement but does not alter hypoxia-induced decreases in NPR-C and suggest that
compensatory increases in BNP expression occur in the absence of ANP.
pulmonary hypertension
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