Key result
AngII infusion fails to reduce renal NE despite causing cardiac sympathetic nerve loss.
Why the study?
AngII infusion was known to cause sympathetic nerve loss in the heart, but whether it had a similar effect on sympathetic nerves in the kidneys was unknown.
Does Angiotensin II infusion reduce sympathetic nerve content in the kidneys in mice?
Does Angiotensin II infusion reduce sympathetic nerve content in the kidneys in mice?
Answers are grounded in this paper and cite their sources.
While Angiotensin II infusion causes hypertension and rapid sympathetic nerve loss in the heart, it does not trigger similar sympathetic denervation in the kidneys.
Objective: Angiotensin II (AngII) is a critical player in the regulation of blood pressure. Elevated AngII increases blood pressure and high blood pressure can lead to heart failure. We previously used AngII to induce hypertension and heart failure in mice and discovered it led to low norepinephrine (NE) content and sympathetic nerve loss (denervation) in the heart after 4 weeks of AngII treatment. Follow up studies identified cardiac nerve loss after just one week of AngII infusion. AngII raises blood pressure through actions in the kidney, and the focus of this study was to determine if one week of Ang II had a similar effect on sympathetic nerves in the kidneys. Experimental Procedure: 13–16-week-old C57Bl6J mice were implanted with minipumps loaded with Ang II (700 ng/kg*min) or saline as a control. Blood pressure measurements were done in all mice to confirm AngII induced hypertension. “Hypertension” was defined by a MAP (Mean Arterial Pressure) 120. After one week of AngII infusion kidneys and hearts were harvested and frozen. Additional hearts were fixed in paraformaldehyde. NE was extracted from pulverized kidney and heart tissue with 0.1 M perchloric acid. NE and the normalization control DHBA (dihydroxybenzylamine) were alumina precipitated to concentrate them for analysis. NE and DHBA were quantified by high performance liquid chromatography with electrochemical detection (HPLC-ED). Cardiac innervation was identified using immunohistochemistry for tyrosine hydroxylase and quantified using ImageJ. Results: The AngII did induce hypertension in the mice with average MAP scores of 142±14 mmHg (Mean±SD, n=5) compared to saline controls (93±17 mmHg, Mean±SD, n=9). The HPLC-EC data showed no significant loss of NE in the kidneys: 4.5±1.7 pmol/mg (AngII; Mean±SD, n=7) and 4.5± 0.5 pmol/mg (control; Mean±SD, n=7). In contrast, NE levels in the heart strongly indicated denervation of the left ventricle with AngII NE content 0.95±.85 pmol/m[GU1] g (Mean±SD, n=7) compared to saline controls 6.7±2.2 pmol/mg (Mean±SD, n=5) Immunohistochemistry for tyrosine hydroxylase confirmed the loss of sympathetic nerves in the left ventricle (0.3±0.2%, Mean±SD, n=5) compared to saline controls (1.0±0.1%, Mean±SD, n=9). Conclusions: AngII stimulates increased blood pressure via effects in the kidney, but doses of AngII that cause sympathetic nerve loss in the heart do not trigger sympathetic nerve loss in the kidney. Funding for this project was provided by NIH #HL09305 and an APS SURF fellowship to S.P. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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Pardee et al. (2026) studied Hypertension. Angiotensin II vs. saline was evaluated on norepinephrine (NE) content in the kidneys. One week of Angiotensin II infusion did not cause significant loss of norepinephrine in the kidneys (4.5 vs 4.5 pmol/mg), despite causing sympathetic nerve loss in the heart.
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