Altered regulation of renal interstitial hydrostatic pressure and the renal renin-angiotensin system in the absence of atrial natriuretic peptide.
BACKGROUND
Although it has been well established that atrial natriuretic peptide gene-disrupted (ANP-/-) mice are a useful model of salt-sensitive hypertension, surprisingly little is known about the control of their intrarenal renin-angiotensin system (RAS) and pressure-natriuresis mechanism, key components in blood pressure, fluid and electrolyte regulation. The aim of this study was to determine whether ANP disruption results in changes in the renal and adrenal local RAS and the acute pressure-natriuresis mechanism.


METHODS
Renal and adrenal renin, angiotensin type 1 (AT1)(A and B) and angiotensin type 2 (AT2) receptor messenger RNA expression levels were determined by northern blotting or real time reverse transcriptase-polymerase chain reaction. Plasma aldosterone and renal and adrenal angiotensin II peptide levels were determined by radioimmunoassay. To examine the acute pressure-natriuresis response, changes in renal interstitial hydrostatic pressure (RIHP) were assessed after manipulations of renal arterial pressure (RAP) in anaesthetized mice.


RESULTS
Renal and adrenal renin mRNA and angiotensin II levels were lower in ANP-/- and +/- mice compared with +/+mice. ANP-/- mice also had greater renal AT1A and adrenal AT2 mRNA levels compared with the other genotypes. RAP and RIHP were significantly higher in -/-mice compared with +/+mice. Furthermore, there was a blunted slope of the RAP-RIHP relationship after increases in RAP in ANP-/- mice.


CONCLUSIONS
These data indicate that ANP disruption results in a blunting of the dynamic properties of the acute pressure-natriuresis mechanism at increased levels of RAP, as well as a reduced expression of renal and adrenal local RAS.
O'Tierney
Perrie F
PF
Department of Anatomy and Cell Biology, Canada.
Komolova
Marina
M
Tse
M Yat
MY
Adams
Michael A
MA
Pang
Stephen C
SC
D000311:Adrenal Glands / Q000502:physiology; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D020869:Gene Expression Profiling; D007668:Kidney / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*
D012333:RNA, Messenger; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D000803:Angiotensin I; D012083:Renin