Central depletion of angiotensinogen is associated with elevated AT1 receptors in the SFO and PVN.
The brain renin-angiotensin system (RAS) is important in fluid balance and blood pressure regulation. In this study, we compared angiotensin (Ang) receptor density in the subfornical organ (SFO) and paraventricular nucleus (PVN) of a) brain angiotensinogen deficient rats (ASrAogen); b) those with high levels of brain Ang II [(mRen2)27]; c) Hannover Sprague Dawley (SD) rats at 48 and 68 wks of age. Since there was no difference between the two ages in any of the three strains, the data from the 48 and 68 wk time points were combined. There was a significantly higher level of AT1 receptors in the SFO and PVN of ASrAogen animals compared to both the SD and (mRen2)27 rats. This suggests that the brain RAS is important in regulating receptor density and that the differences may be explained by lower levels of the peptide locally. These higher levels of receptors suggest that the ASrAogen animals in adulthood and early aging would be more sensitive to either circulating or endogenous brain Ang II than the SD animals of similar age. In contrast, the similar receptor density in the (mRen2)27 and SD rats suggest that previous reports of reduced responses in the (mRen2)27 rats may result from differences in post receptor mechanisms such as intracellular signaling. Moreover, our data reveal that functional assessments are necessary in addition to receptor density levels to understand the consequences of long-term alterations in brain tissue peptides.
Kasper
Sherry O
SO
The Hypertension and Vascular Disease Center and Physiology/Pharmacology Department, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA.
Ferrario
Carlos M
CM
Ganten
Detlev
D
Diz
Debra I
DI
D000804:Angiotensin II / Q000096:biosynthesis / Q000235:genetics; D000808:Angiotensinogen / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D013045:Species Specificity; D013356:Subfornical Organ / Q000378:metabolism*
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D000804:Angiotensin II