Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP

J. R. Klinger, R. D. Petit, L. A. Curtin, R. R. Warburton, D. S. Wrenn, M. E. Steinhelper, Loren Field, N. S. Hill

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Elevated plasma atrial natriuretic peptide (ANP) levels have been shown to blunt pulmonary hemodynamic responses to chronic hypoxia, but whether elevated circulating ANP levels negatively feedback on cardiac expression of the ANP gene is unknown. Using a recently developed strain of transgenic mouse (TTR-ANF) that expresses a transthyretin promoter-ANP fusion gene in the liver, we studied the effect of chronically elevated plasma ANP levels on cardiac hypertrophic and pulmonary hemodynamic responses and expression of the endogenous cardiac ANP gene during chronic hypoxia. Plasma ANP levels were 10-fold higher in TTR-ANF mice than in their non-transgenic littermates. After 3 wk of hypobaric hypoxia (0.5 atm), right ventricular hypertrophy and pulmonary hypertension had developed in both groups of mice, but TTR-ANF mice had lower right ventricle-to-left ventricle plus septum weight ratios (0.39 ± 0.01 vs. 0.45 ± 0.02), right ventricular systolic pressures (25 ± 2 vs. 29 ± 2 mmHg), and lung dry weight-to-body weight ratios (0.48 ± 0.03 vs. 0.57 ± 0.01 mg/g) and less muscularization of peripheral pulmonary vessels (8.3 ± 1.4 vs. 17.4 ± 2.5%) than nontransgenic controls. Right atrial and ventricular steady-state ANP mRNA levels were the same in both groups of mice under normoxic and hypoxic conditions despite much higher plasma ANP levels and less pulmonary hypertension in TTR-ANF mice. We conclude that chronically elevated plasma ANP levels attenuate the development of hypoxic pulmonary hypertension in mice but do not suppress cardiac expression of the endogenous ANP gene under normoxic conditions nor blunt the upregulation of right ventricular ANP expression during chronic hypoxia.

Original languageEnglish (US)
Pages (from-to)198-205
Number of pages8
JournalJournal of Applied Physiology
Volume75
Issue number1
StatePublished - 1993
Externally publishedYes

Fingerprint

Atrial Natriuretic Factor
Transgenic Mice
Pulmonary Hypertension
Lung
Hypoxia
Heart Ventricles
Hemodynamics
Genes
Right Ventricular Hypertrophy
Weights and Measures
Prealbumin
Gene Fusion
Ventricular Pressure

Keywords

  • atrial natriuretic peptide
  • cardiac hypertrophy
  • gene expression
  • pulmonary hypertension

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Klinger, J. R., Petit, R. D., Curtin, L. A., Warburton, R. R., Wrenn, D. S., Steinhelper, M. E., ... Hill, N. S. (1993). Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP. Journal of Applied Physiology, 75(1), 198-205.

Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP. / Klinger, J. R.; Petit, R. D.; Curtin, L. A.; Warburton, R. R.; Wrenn, D. S.; Steinhelper, M. E.; Field, Loren; Hill, N. S.

In: Journal of Applied Physiology, Vol. 75, No. 1, 1993, p. 198-205.

Research output: Contribution to journalArticle

Klinger, JR, Petit, RD, Curtin, LA, Warburton, RR, Wrenn, DS, Steinhelper, ME, Field, L & Hill, NS 1993, 'Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP', Journal of Applied Physiology, vol. 75, no. 1, pp. 198-205.
Klinger JR, Petit RD, Curtin LA, Warburton RR, Wrenn DS, Steinhelper ME et al. Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP. Journal of Applied Physiology. 1993;75(1):198-205.
Klinger, J. R. ; Petit, R. D. ; Curtin, L. A. ; Warburton, R. R. ; Wrenn, D. S. ; Steinhelper, M. E. ; Field, Loren ; Hill, N. S. / Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP. In: Journal of Applied Physiology. 1993 ; Vol. 75, No. 1. pp. 198-205.
@article{05592a43af714af0b8526d4375524c44,
title = "Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP",
abstract = "Elevated plasma atrial natriuretic peptide (ANP) levels have been shown to blunt pulmonary hemodynamic responses to chronic hypoxia, but whether elevated circulating ANP levels negatively feedback on cardiac expression of the ANP gene is unknown. Using a recently developed strain of transgenic mouse (TTR-ANF) that expresses a transthyretin promoter-ANP fusion gene in the liver, we studied the effect of chronically elevated plasma ANP levels on cardiac hypertrophic and pulmonary hemodynamic responses and expression of the endogenous cardiac ANP gene during chronic hypoxia. Plasma ANP levels were 10-fold higher in TTR-ANF mice than in their non-transgenic littermates. After 3 wk of hypobaric hypoxia (0.5 atm), right ventricular hypertrophy and pulmonary hypertension had developed in both groups of mice, but TTR-ANF mice had lower right ventricle-to-left ventricle plus septum weight ratios (0.39 ± 0.01 vs. 0.45 ± 0.02), right ventricular systolic pressures (25 ± 2 vs. 29 ± 2 mmHg), and lung dry weight-to-body weight ratios (0.48 ± 0.03 vs. 0.57 ± 0.01 mg/g) and less muscularization of peripheral pulmonary vessels (8.3 ± 1.4 vs. 17.4 ± 2.5{\%}) than nontransgenic controls. Right atrial and ventricular steady-state ANP mRNA levels were the same in both groups of mice under normoxic and hypoxic conditions despite much higher plasma ANP levels and less pulmonary hypertension in TTR-ANF mice. We conclude that chronically elevated plasma ANP levels attenuate the development of hypoxic pulmonary hypertension in mice but do not suppress cardiac expression of the endogenous ANP gene under normoxic conditions nor blunt the upregulation of right ventricular ANP expression during chronic hypoxia.",
keywords = "atrial natriuretic peptide, cardiac hypertrophy, gene expression, pulmonary hypertension",
author = "Klinger, {J. R.} and Petit, {R. D.} and Curtin, {L. A.} and Warburton, {R. R.} and Wrenn, {D. S.} and Steinhelper, {M. E.} and Loren Field and Hill, {N. S.}",
year = "1993",
language = "English (US)",
volume = "75",
pages = "198--205",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP

AU - Klinger, J. R.

AU - Petit, R. D.

AU - Curtin, L. A.

AU - Warburton, R. R.

AU - Wrenn, D. S.

AU - Steinhelper, M. E.

AU - Field, Loren

AU - Hill, N. S.

PY - 1993

Y1 - 1993

N2 - Elevated plasma atrial natriuretic peptide (ANP) levels have been shown to blunt pulmonary hemodynamic responses to chronic hypoxia, but whether elevated circulating ANP levels negatively feedback on cardiac expression of the ANP gene is unknown. Using a recently developed strain of transgenic mouse (TTR-ANF) that expresses a transthyretin promoter-ANP fusion gene in the liver, we studied the effect of chronically elevated plasma ANP levels on cardiac hypertrophic and pulmonary hemodynamic responses and expression of the endogenous cardiac ANP gene during chronic hypoxia. Plasma ANP levels were 10-fold higher in TTR-ANF mice than in their non-transgenic littermates. After 3 wk of hypobaric hypoxia (0.5 atm), right ventricular hypertrophy and pulmonary hypertension had developed in both groups of mice, but TTR-ANF mice had lower right ventricle-to-left ventricle plus septum weight ratios (0.39 ± 0.01 vs. 0.45 ± 0.02), right ventricular systolic pressures (25 ± 2 vs. 29 ± 2 mmHg), and lung dry weight-to-body weight ratios (0.48 ± 0.03 vs. 0.57 ± 0.01 mg/g) and less muscularization of peripheral pulmonary vessels (8.3 ± 1.4 vs. 17.4 ± 2.5%) than nontransgenic controls. Right atrial and ventricular steady-state ANP mRNA levels were the same in both groups of mice under normoxic and hypoxic conditions despite much higher plasma ANP levels and less pulmonary hypertension in TTR-ANF mice. We conclude that chronically elevated plasma ANP levels attenuate the development of hypoxic pulmonary hypertension in mice but do not suppress cardiac expression of the endogenous ANP gene under normoxic conditions nor blunt the upregulation of right ventricular ANP expression during chronic hypoxia.

AB - Elevated plasma atrial natriuretic peptide (ANP) levels have been shown to blunt pulmonary hemodynamic responses to chronic hypoxia, but whether elevated circulating ANP levels negatively feedback on cardiac expression of the ANP gene is unknown. Using a recently developed strain of transgenic mouse (TTR-ANF) that expresses a transthyretin promoter-ANP fusion gene in the liver, we studied the effect of chronically elevated plasma ANP levels on cardiac hypertrophic and pulmonary hemodynamic responses and expression of the endogenous cardiac ANP gene during chronic hypoxia. Plasma ANP levels were 10-fold higher in TTR-ANF mice than in their non-transgenic littermates. After 3 wk of hypobaric hypoxia (0.5 atm), right ventricular hypertrophy and pulmonary hypertension had developed in both groups of mice, but TTR-ANF mice had lower right ventricle-to-left ventricle plus septum weight ratios (0.39 ± 0.01 vs. 0.45 ± 0.02), right ventricular systolic pressures (25 ± 2 vs. 29 ± 2 mmHg), and lung dry weight-to-body weight ratios (0.48 ± 0.03 vs. 0.57 ± 0.01 mg/g) and less muscularization of peripheral pulmonary vessels (8.3 ± 1.4 vs. 17.4 ± 2.5%) than nontransgenic controls. Right atrial and ventricular steady-state ANP mRNA levels were the same in both groups of mice under normoxic and hypoxic conditions despite much higher plasma ANP levels and less pulmonary hypertension in TTR-ANF mice. We conclude that chronically elevated plasma ANP levels attenuate the development of hypoxic pulmonary hypertension in mice but do not suppress cardiac expression of the endogenous ANP gene under normoxic conditions nor blunt the upregulation of right ventricular ANP expression during chronic hypoxia.

KW - atrial natriuretic peptide

KW - cardiac hypertrophy

KW - gene expression

KW - pulmonary hypertension

UR - http://www.scopus.com/inward/record.url?scp=0027179449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027179449&partnerID=8YFLogxK

M3 - Article

C2 - 7690745

AN - SCOPUS:0027179449

VL - 75

SP - 198

EP - 205

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 1

ER -