Angiotensin-(1-7) in paraventricular nucleus modulates sympathetic activity and cardiac sympathetic afferent reflex in renovascular hypertensive rats.

Abstract

BACKGROUND:

Excessive sympathetic activity contributes to the pathogenesis and progression of hypertension. Enhanced cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation. This study was designed to determine the roles of angiotensin (Ang)-(1-7) in paraventricular nucleus (PVN) in modulating sympathetic activity and CSAR and its signal pathway in renovascular hypertension.

METHODOLOGY/PRINCIPAL FINDINGS:

Renovascular hypertension was induced with two-kidney, one-clip method. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and cervical-vagotomized rats with anesthesia. CSAR was evaluated with the RSNA and MAP responses to epicardial application of capsaicin. PVN microinjection of Ang-(1-7) and cAMP analogue db-cAMP caused greater increases in RSNA and MAP, and enhancement in CSAR in hypertensive rats than in sham-operated rats, while Mas receptor antagonist A-779 produced opposite effects. There was no significant difference in the angiotensin-converting enzyme 2 (ACE2) activity and Ang-(1-7) level in the PVN between sham-operated rats and hypertensive rats, but the Mas receptor protein expression in the PVN was increased in hypertensive rats. The effects of Ang-(1-7) were abolished by A-779, adenylyl cyclase inhibitor SQ22536 or protein kinase A (PKA) inhibitor Rp-cAMP. SQ22536 or Rp-cAMP reduced RSNA and MAP in hypertensive rats, and attenuated the CSAR in both sham-operated and hypertensive rats.

CONCLUSIONS:

Ang-(1-7) in the PVN increases RSNA and MAP and enhances the CSAR, which is mediated by Mas receptors. Endogenous Ang-(1-7) and Mas receptors contribute to the enhanced sympathetic outflow and CSAR in renovascular hypertension. A cAMP-PKA pathway is involved in the effects of Ang-(1-7) in the PVN.

• Authors: Ying Han, Hai-Jian Sun, Peng Li, Qing Gao, Ye-bo Zhou, Feng Zhang, Xing-Ya Gao, Guo-Qing Zhu
• Journal: PloS one (PLoS One) Vol. 7 Issue 11 Pg. e48966 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23139827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 7-Ala-angiotensin (1-7)
• Peptide Fragments
• Proto-Oncogene Mas
• Proto-Oncogene Proteins
• Receptors, G-Protein-Coupled
• Thionucleotides
• Angiotensin II
• 9-(tetrahydro-2-furyl)-adenine
• adenosine-3',5'-cyclic phosphorothioate
• Bucladesine
• Angiotensin I
• Cyclic AMP
• Peptidyl-Dipeptidase A
• Ace2 protein, rat
• Angiotensin-Converting Enzyme 2
• angiotensin I (1-7)
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Afferent Pathways (drug effects, physiopathology)
• Angiotensin I (pharmacology)
• Angiotensin II (analogs & derivatives, pharmacology)
• Angiotensin-Converting Enzyme 2
• Animals
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Bucladesine (pharmacology)
• Cyclic AMP (analogs & derivatives, pharmacology)
• Heart (drug effects, innervation, physiopathology)
• Hypertension, Renovascular (pathology, physiopathology)
• Kidney (drug effects, innervation, physiopathology)
• Male
• Microinjections
• Paraventricular Hypothalamic Nucleus (drug effects, pathology, physiopathology)
• Peptide Fragments (pharmacology)
• Peptidyl-Dipeptidase A (metabolism)
• Proto-Oncogene Mas
• Proto-Oncogene Proteins (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, G-Protein-Coupled (metabolism)
• Reflex (drug effects)
• Sympathetic Nervous System (drug effects, pathology, physiopathology)
• Thionucleotides (pharmacology)