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1 Hypertension and Vascular Disease Center and Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
2 Charite-University Medicine Berlin, Berlin, Germany
3 Physiology and Pharmacology, Ponce School of Medicine, Ponce, Puerto Rico
* To whom correspondence should be addressed. E-mail: ddiz{at}wfubmc.edu.
Transgenic rats with targeted decreased glial expression of angiotensinogen [ASrAogen] did not show an increase in systolic pressure in comparison to Sprague Dawley (SD) rats during aging (15 to 69 weeks of age). ASrAogen animals had lower body weights throughout the study, similar to reports for animals with systemic knock-out of angiotensinogen or treated long-term with renin-angiotensin system (RAS) blockers. Further characterization of indices of growth and metabolism in the ASrAogen rats in comparison with (mRen2)27 and SD rats, that express elevated versus normal brain and tissue angiotensin II levels, respectively, revealed that serum leptin was 100 - 200% higher in SD and (mRen2)27 at 46 wk and 69 wk of age. Consistent with low serum leptin, ASrAogen rats had higher food intake (73%) compared with SD or (mRen2)27 rats. (mRen2)27 rats had higher resting insulin levels than ASrAogen rats at all ages. Insulin levels were constant during aging in ASrAogen rats, whereas an increase occurred in SD rats, leading to higher insulin levels at 46 wk and 69 wk of age compared with ASrAogen rats. IGF-1 was comparable among strains at all ages, but (mRen2)27 had longer and ASrAogen had shorter tail length versus SD rats at 15 weeks of age. In conclusion, reduced expression of glial angiotensinogen blunts the age-dependent rise in insulin levels and weight gain, findings that mimic effects of long-term systemic blockade of the RAS or systemic knock-out of angiotensinogen. These data implicate glial angiotensinogen in the regulation of body metabolism as well as hormonal mechanisms regulating blood pressure.
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