Upregulation of ANP and NPR-C mRNA in the kidney and heart of eNOS knockout mice.
OBJECTIVE
The aim of the present studywas to examine the question of whether the atrial natriuretic peptide (ANP) system is altered by endothelial nitric-oxide synthase (eNOS).


METHODS
Male eNOS-deficient mice (eNOS-/-) and wild type control mice (eNOS+/+, C57B1/6J) were used. Blood pressure was measured in anesthetized mice by tail cuff plethysmography and renal function was measured. Expression of ANP, natriuretic peptide receptor (NPR)-A, NPR-C, and tonicity-responsive enhancer binding protein (TonEBP) mRNA was determined by real-time PCR. Localization of (125)I-ANP binding sites was measured using in vitro autoradiography.


RESULTS
In eNOS-/- mice, systolic blood pressure increased and left ventricular hypertrophy was observed. Urine volume and osmolarity did not change. Expression of ANP markedly increased in the heart and kidney of eNOS-/- mice. Expression of NPR-A and NPR-C increased in the heart and tended to increase in the kidney of eNOS-/- mice. In the renal medulla in particular, increased expression of NPR-C was more prominent. Expression of TonEBP mRNA was markedly decreased in the renal medulla, but not in the renal cortex. Maximum binding capacity (B(max)) of ANP and C-ANP increased in the renal medulla in eNOS-/- mice.


CONCLUSIONS
These results suggest that the eNOS-NO system may be partly involved in regulation of ANP, NPR-A, -C, and TonEBP mRNA expression in the kidney.
Yuan
Kuichang
K
Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju 561-180, Republic of Korea.
Kim
Sun Young
SY
Oh
Young-Bin
YB
Yu
Jiahua
J
Shah
Amin
A
Park
Byung Hyun
BH
Kim
Suhn Hee
SH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
C492200:Nfat5 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D009320:Atrial Natriuretic Factor; D052250:Nitric Oxide Synthase Type III; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C