Angiotensin-(1-7) in Paraventricular Nucleus Contributes to the Enhanced Cardiac Sympathetic Afferent Reflex and Sympathetic Activity in Chronic Heart Failure Rats.

Abstract

BACKGROUND/AIMS:

Cardiac sympathetic afferent reflex (CSAR) enhancement contributes to exaggerated sympathetic activation in chronic heart failure (CHF). The current study aimed to investigate the roles of angiotensin (Ang)-(1-7) in CSAR modulation and sympathetic activation and Ang-(1-7) signaling pathway in paraventricular nucleus of CHF rats.

METHODS:

CHF was induced by coronary artery ligation. Responses of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to epicardial application of capsaicin were used to evaluate CSAR in rats with anesthesia.

RESULTS:

Ang-(1-7) increased RSNA, MAP, CSAR activity, cAMP level, NAD(P)H oxidase activity and superoxide anion level more significantly in CHF than in sham-operated rats, while Mas receptor antagonist A-779 had the opposite effects. Moreover, Ang-(1-7) augmented effects of Ang II in CHF rats. The effects of Ang-(1-7) were blocked by A-779, adenylyl cyclase inhibitor SQ22536, protein kinase A inhibitor Rp-cAMP, superoxide anion scavenger tempol and NAD(P)H oxidase inhibitor apocynin. Mas and AT1 receptor protein expressions, Ang-(1-7) and Ang II levels in CHF increased.

CONCLUSIONS:

These results indicate that Ang-(1-7) in paraventricular nucleus enhances CSAR and sympathetic output not only by exerting its own effects but also by augmenting the effects of Ang II through Mas receptor in CHF. Endogenous Ang-(1-7)/Mas receptor activity contributes to CSAR enhancement and sympathetic activation in CHF, and NAD(P)H oxidase-derived superoxide anions and the cAMP-PKA signaling pathway are involved in mediating the effects of Ang-(1-7) in CHF.

• Authors: Xingsheng Ren, Feng Zhang, Mingxia Zhao, Zhenzhen Zhao, Shuo Sun, Dustin R Fraidenburg, Haiyang Tang, Ying Han
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 42 Issue 6 Pg. 2523-2539 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 28848201 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• 7-Ala-angiotensin (1-7)
• Acetophenones
• Cyclic N-Oxides
• Peptide Fragments
• Spin Labels
• Superoxides
• Angiotensin II
• Angiotensin I
• acetovanillone
• Cyclic AMP
• NADPH Oxidases
• Cyclic AMP-Dependent Protein Kinases
• angiotensin I (1-7)
• Capsaicin
• tempol
• NG-Nitroarginine Methyl Ester

Topics

• Acetophenones (pharmacology)
• Angiotensin I (pharmacology)
• Angiotensin II (analogs & derivatives, metabolism, pharmacology)
• Animals
• Arterial Pressure (drug effects)
• Capsaicin (pharmacology)
• Cyclic AMP (metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Cyclic N-Oxides (pharmacology)
• Heart Failure
• Hemodynamics (drug effects)
• Kidney (drug effects, metabolism)
• Male
• NADPH Oxidases (metabolism)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Paraventricular Hypothalamic Nucleus (drug effects, metabolism)
• Peptide Fragments (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Spin Labels
• Superoxides (metabolism)
• Sympathetic Nervous System (drug effects, metabolism)