Expression of B-type natriuretic peptide in atrial natriuretic peptide gene disrupted mice.
Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are two hormones produced and secreted by the heart to control blood pressure, body fluid homeostasis and electrolyte balance. Each peptide binds to a common family of 3 receptors (GC-A, GC-B and C-receptor) with varying degrees of affinity. The proANP gene disrupted mouse model provides an excellent opportunity to examine the regulation and expression of BNP in the absence ofANP. A new radioimmunoassay (RIA) was developed in order to measure mouse BNP peptide levels in the plasma, atrium and ventricle of the mouse. A detection limit of 3-6 pg/tube was achieved by this assay. Results show that plasma and ventricular level of BNP were unchanged among the three genotypes of mice. However, a significant decrease in the BNP level was noted in the atrium. The homozygous mutant (ANP-/-) had undetectable levels of BNP in the atrium, while the heterozygous (ANP+/-) and wild-type (ANP+/+) mice had 430 and 910 pg/mg in the atrium, respectively. Northern Blot analysis shows the ANP-/- mice has a 40% reduction of BNP mRNA level in the atrium and a 5-fold increase in the ventricle as compared with that of the ANP+/+ mouse. Our data suggest that there is a compensatory response of BNP expression to proANP gene disruption. Despite the changes in the atrial and ventricular tissue mRNA and peptide levels, the plasma BNP level remains unaltered in the ANP-/- mice. We conclude that the inability of BNP to completely compensate for the lack of ANP eventually leads to chronic hypertension in the proANP gene disrupted mice.
Tse
M Y
MY
Department of Anatomy and Cell Biology, Queen 's University, Kingston, Ontario, Canada.
Watson
J D
JD
Sarda
I R
IR
Flynn
T G
TG
Pang
S C
SC
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D015152:Blotting, Northern; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003429:Cross Reactions; D005786:Gene Expression Regulation; D005838:Genotype; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D020097:Natriuretic Peptide, Brain; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D012680:Sensitivity and Specificity
D002316:Cardiotonic Agents; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor