Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Hong Zheng, Xuefei Liu, Neeru M. Sharma, Kaushik P. Patel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β 1 - and β 2 -adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β 1 -adrenoceptor (by 47%) and β 2 -adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and -dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.

Original languageEnglish (US)
Pages (from-to)H337-H346
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume311
Issue number2
DOIs
StatePublished - Aug 2016

Fingerprint

Denervation
Adrenergic Receptors
Heart Failure
Kidney
Heart Ventricles
Blood Pressure
Adrenergic Agonists
Brain Natriuretic Peptide
Isoproterenol
Adrenergic Agents
Ligation
Sprague Dawley Rats
Coronary Vessels
Norepinephrine
Reference Values
Proteins
Collagen
Hemodynamics

Keywords

  • Cardiac function
  • Heart failure
  • Renal nerve
  • Sympathetic nerve activity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Renal denervation improves cardiac function in rats with chronic heart failure : Effects on expression of β-adrenoceptors. / Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.; Patel, Kaushik P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 311, No. 2, 08.2016, p. H337-H346.

Research output: Contribution to journalArticle

@article{f1cb9489393f4e8989df8923598bd256,
title = "Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors",
abstract = "Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30{\%} of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β 1 - and β 2 -adrenoceptor proteins in the left ventricle were reduced by 37 and 49{\%}, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β 1 -adrenoceptor (by 47{\%}) and β 2 -adrenoceptor (by 100{\%}) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71{\%}) and -dP/dt (by 62{\%}) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.",
keywords = "Cardiac function, Heart failure, Renal nerve, Sympathetic nerve activity",
author = "Hong Zheng and Xuefei Liu and Sharma, {Neeru M.} and Patel, {Kaushik P.}",
year = "2016",
month = "8",
doi = "10.1152/ajpheart.00999.2015",
language = "English (US)",
volume = "311",
pages = "H337--H346",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Renal denervation improves cardiac function in rats with chronic heart failure

T2 - Effects on expression of β-adrenoceptors

AU - Zheng, Hong

AU - Liu, Xuefei

AU - Sharma, Neeru M.

AU - Patel, Kaushik P.

PY - 2016/8

Y1 - 2016/8

N2 - Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β 1 - and β 2 -adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β 1 -adrenoceptor (by 47%) and β 2 -adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and -dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.

AB - Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β 1 - and β 2 -adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β 1 -adrenoceptor (by 47%) and β 2 -adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and -dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.

KW - Cardiac function

KW - Heart failure

KW - Renal nerve

KW - Sympathetic nerve activity

UR - http://www.scopus.com/inward/record.url?scp=84983637764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983637764&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00999.2015

DO - 10.1152/ajpheart.00999.2015

M3 - Article

C2 - 27288440

AN - SCOPUS:84983637764

VL - 311

SP - H337-H346

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 2

ER -