nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure

Yu Wang, Kaushik P Patel, Kurtis G. Cornish, Keith M. Channon, Irving H Zucker

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

We hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant adenovirus, either Ad.nNOS or Ad.β-Gal, was transfected into the RVLM. nNOS expression in the RVLM was confirmed by Western blot analysis, NADPH-diaphorase, and immunohistochemical staining. We studied baroreflex control of the heart rate (HR) and renal sympathetic nerve activity (RSNA) in the anesthetized state 3 days after gene transfer by intravenous injections of phenylephrine and nitroprusside. Baroreflex sensitivity was depressed for HR and RSNA regulation in CHF rats (2.0 ± 0.3 vs. 0.8 ± 0.2 beats·min -1·mmHg-1, P < 0.01 and 3.8 ± 0.3 vs. 1. 2 ± 0.1% max/mmHg, P < 0.01, respectively). Ad.nNOS transfer into RVLM significantly increased the HR and RSNA ranges (152 ± 19 vs. 94 ± 12 beats/min, P < 0.05 and 130 ± 16 vs. 106 ± 5% max/mmHg, P < 0.05) compared with the Ad.β-Gal in CHF rats. Ad.nNOS also improved the baroreflex gain for the control of HR and RSNA (1.8 ± 0.2 vs. 0.8 ± 0.2 beats·min-1·mmHg -1, P < 0.01 and 2.6 ± 0.2 vs. 1.2 ± 0.1% max/mmHg, P < 0.01). In sham-operated rats, we found that Ad.nNOS transfer enhanced the HR range compared with Ad.β-Gal gene transfer (188 ± 15 vs. 127 ± 14 beats/min, P < 0.05) but did not alter any other parameter. This study represents the first demonstration of altered baroreflex function following increases in central nNOS in the CHF state. We conclude that delivery of Ad.nNOS into the RVLM improves baroreflex function in rats with CHF.

Original languageEnglish (US)
Pages (from-to)H1660-H1667
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number4 54-4
StatePublished - Oct 1 2003

Fingerprint

Nitric Oxide Synthase Type I
Baroreflex
Heart Failure
Heart Rate
Genes
Kidney
NADPH Dehydrogenase
Nitroprusside
Phenylephrine
Adenoviridae
Intravenous Injections
Ligation
Coronary Vessels
Hemodynamics
Western Blotting
Staining and Labeling

Keywords

  • Adenovirus
  • Heart rate
  • Nitric oxide
  • Sympathetic nerve activity

ASJC Scopus subject areas

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

Cite this

nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. / Wang, Yu; Patel, Kaushik P; Cornish, Kurtis G.; Channon, Keith M.; Zucker, Irving H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 4 54-4, 01.10.2003, p. H1660-H1667.

Research output: Contribution to journalArticle

@article{2c46c2fc2e9248b4a50d9c9d61c270d1,
title = "nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure",
abstract = "We hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant adenovirus, either Ad.nNOS or Ad.β-Gal, was transfected into the RVLM. nNOS expression in the RVLM was confirmed by Western blot analysis, NADPH-diaphorase, and immunohistochemical staining. We studied baroreflex control of the heart rate (HR) and renal sympathetic nerve activity (RSNA) in the anesthetized state 3 days after gene transfer by intravenous injections of phenylephrine and nitroprusside. Baroreflex sensitivity was depressed for HR and RSNA regulation in CHF rats (2.0 ± 0.3 vs. 0.8 ± 0.2 beats·min -1·mmHg-1, P < 0.01 and 3.8 ± 0.3 vs. 1. 2 ± 0.1{\%} max/mmHg, P < 0.01, respectively). Ad.nNOS transfer into RVLM significantly increased the HR and RSNA ranges (152 ± 19 vs. 94 ± 12 beats/min, P < 0.05 and 130 ± 16 vs. 106 ± 5{\%} max/mmHg, P < 0.05) compared with the Ad.β-Gal in CHF rats. Ad.nNOS also improved the baroreflex gain for the control of HR and RSNA (1.8 ± 0.2 vs. 0.8 ± 0.2 beats·min-1·mmHg -1, P < 0.01 and 2.6 ± 0.2 vs. 1.2 ± 0.1{\%} max/mmHg, P < 0.01). In sham-operated rats, we found that Ad.nNOS transfer enhanced the HR range compared with Ad.β-Gal gene transfer (188 ± 15 vs. 127 ± 14 beats/min, P < 0.05) but did not alter any other parameter. This study represents the first demonstration of altered baroreflex function following increases in central nNOS in the CHF state. We conclude that delivery of Ad.nNOS into the RVLM improves baroreflex function in rats with CHF.",
keywords = "Adenovirus, Heart rate, Nitric oxide, Sympathetic nerve activity",
author = "Yu Wang and Patel, {Kaushik P} and Cornish, {Kurtis G.} and Channon, {Keith M.} and Zucker, {Irving H}",
year = "2003",
month = "10",
day = "1",
language = "English (US)",
volume = "285",
pages = "H1660--H1667",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "4 54-4",

}

TY - JOUR

T1 - nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure

AU - Wang, Yu

AU - Patel, Kaushik P

AU - Cornish, Kurtis G.

AU - Channon, Keith M.

AU - Zucker, Irving H

PY - 2003/10/1

Y1 - 2003/10/1

N2 - We hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant adenovirus, either Ad.nNOS or Ad.β-Gal, was transfected into the RVLM. nNOS expression in the RVLM was confirmed by Western blot analysis, NADPH-diaphorase, and immunohistochemical staining. We studied baroreflex control of the heart rate (HR) and renal sympathetic nerve activity (RSNA) in the anesthetized state 3 days after gene transfer by intravenous injections of phenylephrine and nitroprusside. Baroreflex sensitivity was depressed for HR and RSNA regulation in CHF rats (2.0 ± 0.3 vs. 0.8 ± 0.2 beats·min -1·mmHg-1, P < 0.01 and 3.8 ± 0.3 vs. 1. 2 ± 0.1% max/mmHg, P < 0.01, respectively). Ad.nNOS transfer into RVLM significantly increased the HR and RSNA ranges (152 ± 19 vs. 94 ± 12 beats/min, P < 0.05 and 130 ± 16 vs. 106 ± 5% max/mmHg, P < 0.05) compared with the Ad.β-Gal in CHF rats. Ad.nNOS also improved the baroreflex gain for the control of HR and RSNA (1.8 ± 0.2 vs. 0.8 ± 0.2 beats·min-1·mmHg -1, P < 0.01 and 2.6 ± 0.2 vs. 1.2 ± 0.1% max/mmHg, P < 0.01). In sham-operated rats, we found that Ad.nNOS transfer enhanced the HR range compared with Ad.β-Gal gene transfer (188 ± 15 vs. 127 ± 14 beats/min, P < 0.05) but did not alter any other parameter. This study represents the first demonstration of altered baroreflex function following increases in central nNOS in the CHF state. We conclude that delivery of Ad.nNOS into the RVLM improves baroreflex function in rats with CHF.

AB - We hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant adenovirus, either Ad.nNOS or Ad.β-Gal, was transfected into the RVLM. nNOS expression in the RVLM was confirmed by Western blot analysis, NADPH-diaphorase, and immunohistochemical staining. We studied baroreflex control of the heart rate (HR) and renal sympathetic nerve activity (RSNA) in the anesthetized state 3 days after gene transfer by intravenous injections of phenylephrine and nitroprusside. Baroreflex sensitivity was depressed for HR and RSNA regulation in CHF rats (2.0 ± 0.3 vs. 0.8 ± 0.2 beats·min -1·mmHg-1, P < 0.01 and 3.8 ± 0.3 vs. 1. 2 ± 0.1% max/mmHg, P < 0.01, respectively). Ad.nNOS transfer into RVLM significantly increased the HR and RSNA ranges (152 ± 19 vs. 94 ± 12 beats/min, P < 0.05 and 130 ± 16 vs. 106 ± 5% max/mmHg, P < 0.05) compared with the Ad.β-Gal in CHF rats. Ad.nNOS also improved the baroreflex gain for the control of HR and RSNA (1.8 ± 0.2 vs. 0.8 ± 0.2 beats·min-1·mmHg -1, P < 0.01 and 2.6 ± 0.2 vs. 1.2 ± 0.1% max/mmHg, P < 0.01). In sham-operated rats, we found that Ad.nNOS transfer enhanced the HR range compared with Ad.β-Gal gene transfer (188 ± 15 vs. 127 ± 14 beats/min, P < 0.05) but did not alter any other parameter. This study represents the first demonstration of altered baroreflex function following increases in central nNOS in the CHF state. We conclude that delivery of Ad.nNOS into the RVLM improves baroreflex function in rats with CHF.

KW - Adenovirus

KW - Heart rate

KW - Nitric oxide

KW - Sympathetic nerve activity

UR - http://www.scopus.com/inward/record.url?scp=0141453833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141453833&partnerID=8YFLogxK

M3 - Article

C2 - 12969883

AN - SCOPUS:0141453833

VL - 285

SP - H1660-H1667

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 4 54-4

ER -