Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jul;33(7):1401-10.
doi: 10.1097/HJH.0000000000000563.

Effect of angiotensin II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats

Dongze Zhang  1 , Jinxu Liu, Hong Zheng, Huiyin Tu, Robert L Muelleman, Yu-Long Li
Affiliations

Effect of angiotensin II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats

Dongze Zhang et al. J Hypertens. 2015 Jul.

Abstract

Background: Impairment of arterial baroreflex sensitivity is associated with mortality in patients with chronic heart failure (CHF). Elevation of plasma angiotension II (Ang II) contributes to arterial baroreflex dysfunction in CHF. A reduced number of voltage-gated sodium (Nav) channels in aortic baroreceptor neurons are involved in CHF-blunted arterial baroreflex.

Method: In this study, we investigated acute effect of Ang II on Nav currents in the aortic baroreceptor neuron and on arterial baroreflex in sham and coronary artery ligation-induced CHF rats.

Results: Using Ang II I radioimmunoassay, real-time reverse transcription-PCR and western blot, we found that Ang II levels, and mRNA and protein expression of angiotension II type 1 receptor in nodose ganglia from CHF rats were higher than that from sham rats. Local microinjection of Ang II (0.2 nmol) into the nodose ganglia decreased the arterial baroreflex sensitivity in sham rats, whereas losartan (1 nmol, an angiotension II type 1 receptor antagonist) improved the arterial baroreflex sensitivity in CHF rats. Data from patch-clamp recording showed that Ang II (100 nmol/l) acutely inhibited Nav currents in the aortic baroreceptor neurons from sham and CHF rats. In particular, inhibitory effect of Ang II on Nav currents in the aortic baroreceptor neurons was larger in CHF rats than that in sham rats. Losartan (1 μmol/l) totally abolished the inhibitory effect of Ang II on Nav currents in sham and CHF aortic baroreceptor neurons.

Conclusion: These results suggest that elevation of endogenous Ang II in the nodose ganglia contributes to impairment of the arterial baroreflex function in CHF rats through inhibiting Nav channels.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: there are no conflicts of interest.

Disclosures

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig.1
Fig.1
Angiotension II (Ang II) concentration (A) and Ang II type-1 receptor (AT1R) mRNA and protein expression (B–D) in the nodose ganglia (NG) from sham and CHF rats. Data are means ± SE, n=6 rats in each group. *p<0.05 vs. sham.
Fig.2
Fig.2
Arterial baroreflex sensitivity in all experimental groups under anesthesia. Representative recordings (A) and logistic regression curves (B) for reflex changes of heart rate (HR) in response to changes in mean arterial pressure (MAP) from sham, sham +Ang II, CHF, and CHF + losartan rats. C, Quantitative data for maximum gains of HR calculated from logistic regression curves. Phenylephrine (10 μg) was intravenously injected, and Ang II (50 nl, 0.2 nmol) or losartan (50 nl, 1 nmol) was simultaneously microinjected into the NG on both sides. Data are mean ± SE, n=5 rats in each group. *P<0.05 vs. sham; #p<0.05 vs. CHF; † P<0.05 vs. sham + Ang II.
Fig.3
Fig.3
Effect of Ang II on the voltage-gated sodium (Nav) currents in the aortic baroreceptor neurons identified with DiI labeling from sham and CHF rats. A: original Nav currents recording in A-type aortic baroreceptor neurons from sham and CHF rats, with or without Ang II treatment. B and C: Nav currents density-voltage (I–V) curves in A-type (B) and C-type (C) aortic baroreceptor neurons from sham and CHF rats, with or without Ang II treatment; *p<0.05 vs. sham control, #p<0.05 vs. CHF control. D: quantitative data in all groups; *p<0.05 vs. respective control in sham and CHF, #p<0.05 vs. respective Ang II treatment in sham and CHF. E: percentage of Ang II-decreased Nav currents; *P<0.05 vs. sham. Data are mean ± SE; n=4–11 cells from 4–7 rats.
Fig.4
Fig.4
A, representative recordings for steady-state inactivation of the voltage-gated sodium (Nav) channel in A-type aortic baroreceptor neurons from sham and CHF rats. B and C, summary data for steady-state activation and inactivation of the Nav channel in A- and C-type aortic baroreceptor neurons from sham and CHF rats. Data are means ± SE; n= 6–11 cells from 5–7 rats.
See this image and copyright information in PMC

References

    1. Ganguly PK, Beamish RE, Dhalla KS, Innes IR, Dhalla NS. Norepinephrine storage, distribution, and release in diabetic cardiomyopathy. Am J Physiol. 1987;252(6 Pt 1):E734–E739. - PubMed
    1. Lund DD, Subieta AR, Pardini BJ, Chang KS. Alterations in cardiac parasympathetic indices in STZ-induced diabetic rats. Diabetes. 1992;41(2):160–166. - PubMed
    1. Benarroch EE. The arterial baroreflex: functional organization and involvement in neurologic disease. Neurology. 2008;71(21):1733–1738. - PubMed
    1. Czachurski J, Lackner KJ, Ockert D, Seller H. Localization of neurones with baroreceptor input in the medial solitary nucleus by means of intracellular application of horseradish peroxidase in the cat. Neurosci Lett. 1982;28(2):133–137. - PubMed
    1. Spyer KM, Lambert JH, Thomas T. Central nervous system control of cardiovascular function: neural mechanisms and novel modulators. Clin Exp Pharmacol Physiol. 1997;24(9–10):743–747. - PubMed

Publication types

MeSH terms