Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Oct 26, 2019; 11(10): 236-243
Published online Oct 26, 2019. doi: 10.4330/wjc.v11.i10.236
Differential effects of atrial and brain natriuretic peptides on human pulmonary artery: An in vitro study
Azar Hussain, Robert T Bennett, Zaheer Tahir, Emmanuel Isaac, Mubarak A Chaudhry, Syed S Qadri, Mahmoud Loubani, Alyn H Morice
Azar Hussain, Robert T Bennett, Zaheer Tahir, Emmanuel Isaac, Mubarak A Chaudhry, Syed S Qadri, Mahmoud Loubani, Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham HU16 5JQ, United Kingdom
Alyn H Morice, Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Castle Hill Hospital, Cottingham HU16 5JQ, United Kingdom
Author contributions: Hussain A was the principal investigator and was responsible for the design and conduct of the study; Hussain A was responsible for the acquisition, analysis and interpretation of the data and initial draft of the manuscript; Bennett RT, Tahir Z, Isaac E, Chaudhry MA, Qadri SS, Loubani M and Morice AH supervised the study and critically reviewed the article.
Institutional review board statement: The study was reviewed and approved by the North West – Liverpool Central Research Ethics Committee (Approval no: 15/NW/0808).
Informed consent statement: All patients were consulted and consented for resected lung tissue to be studied for our research prior to their operation at the time of their consent for surgery.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Azar Hussain, MBBS, MRCS (Ed), Clinical Research Fellow, Department of Cardiothoracic Surgery, Castle Hill Hospital, Castle Road, Cottingham HU16 5JQ, United Kingdom. azar.hussain@hey.nhs.uk
Telephone: +44-774-8019242
Received: February 10, 2019
Peer-review started: February 12, 2019
First decision: April 11, 2019
Revised: August 31, 2019
Accepted: September 15, 2019
Article in press: September 15, 2019
Published online: October 26, 2019
Abstract
BACKGROUND

The prevalence of cardiovascular diseases, especially heart failure, continues to rise worldwide. In heart failure, increasing levels of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are associated with a worsening of heart failure and a poor prognosis.

AIM

To test whether a high concentration of BNP would inhibit relaxation to ANP.

METHODS

Pulmonary arteries were dissected from disease-free areas of lung resection, as well as pulmonary artery rings of internal diameter 2.5–3.5 mm and 2 mm long, were prepared. Pulmonary artery rings were mounted in a multiwire myograph, and a basal tension of 1.61gf was applied. After equilibration for 60 min, rings were pre-constricted with 11.21 µmol/L PGF2α (EC80), and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.

RESULTS

Although both ANP and BNP were found to vasodilate the pulmonary vessels, ANP is more potent than BNP. pEC50 of ANP and BNP were 8.96 ± 0.21 and 7.54 ± 0.18, respectively, and the maximum efficacy (Emax) for ANP and BNP was -2.03 gf and -0.24 gf, respectively. After addition of BNP, the Emax of ANP reduced from -0.96gf to -0.675gf (P = 0.28).

CONCLUSION

BNP could be acting as a partial agonist in small human pulmonary arteries, and inhibits relaxation to ANP. Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure. This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.

Keywords: Heart failure, Atrial natriuretic peptide, Brain natriuretic peptide, In-vitro, Humans

Core tip: This study demonstrated that both atrial natriuretic peptide and brain natriuretic peptide (BNP) vasodilate isolated human pulmonary artery rings, and that BNP acts as a partial agonist and inhibits the effects of atrial natriuretic peptide. The finding that the addition of BNP inhibits the effects of atrial natriuretic peptide suggests that BNP does act as a partial agonist, and could be advancing the progression to decompensated heart failure.