Inhaled nitric oxide-induced rebound pulmonary hypertension

Role for endothelin-1

D. Michael Mcmullan, Janine M. Bekker, Michael J. Johengen, Kaken Hendricks-Munoz, Rene Gerrets, Stephen Matthew Black, Jeffrey R. Fineman

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Clinically significant increases in pulmonary vascular resistance have been noted on acute withdrawal of inhaled nitric oxide (NO). Endothelin (ET)-1 is a vasoactive peptide produced by the vascular endothelium that may participate in the pathophysiology of pulmonary hypertension. The objectives of this study were to determine the effects of inhaled NO on endogenous ET-1 production in vivo in the intact lamb and to determine the potential role of ET-1 in the rebound pulmonary hypertension associated with the withdrawal of inhaled NO. Seven 1-mo-old vehicle-treated control lambs and six PD-156707 (an ETA receptor antagonist)-treated lambs were mechanically ventilated. Inhaled NO (40 parts per million) was administered for 24 h and then acutely withdrawn. After 24 h of inhaled NO, plasma ET-1 levels increased by 119.5 ± 42.2% (P < 0.05). Western blot analysis revealed that protein levels of pre-proET-1, endothelin-converting enzyme-1α, and ETA and ETB receptors were unchanged. On acute withdrawal of NO, pulmonary vascular resistance (PVR) increased by 77.8% (P < 0.05) in control lambs but was unchanged (-5.5%) in PD-156707-treated lambs. Inhaled NO increased plasma ET-1 concentrations but not gene expression in the intact lamb, and ETA receptor blockade prevented the increase in PVR after NO withdrawal. These data suggest a role for ET-1 in the rebound pulmonary hypertension noted on acute withdrawal of inhaled NO.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number2 49-2
StatePublished - Feb 1 2001

Fingerprint

Endothelin-1
Pulmonary Hypertension
Nitric Oxide
Vascular Resistance
Vascular Endothelium
Western Blotting
Gene Expression
Peptides

Keywords

  • Endothelin receptor
  • Endothelium-derived factors
  • Pulmonary heart disease
  • Pulmonary hypertension of the newborn

ASJC Scopus subject areas

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

Cite this

Mcmullan, D. M., Bekker, J. M., Johengen, M. J., Hendricks-Munoz, K., Gerrets, R., Black, S. M., & Fineman, J. R. (2001). Inhaled nitric oxide-induced rebound pulmonary hypertension: Role for endothelin-1. American Journal of Physiology - Heart and Circulatory Physiology, 280(2 49-2).

Inhaled nitric oxide-induced rebound pulmonary hypertension : Role for endothelin-1. / Mcmullan, D. Michael; Bekker, Janine M.; Johengen, Michael J.; Hendricks-Munoz, Kaken; Gerrets, Rene; Black, Stephen Matthew; Fineman, Jeffrey R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 280, No. 2 49-2, 01.02.2001.

Research output: Contribution to journalArticle

Mcmullan, DM, Bekker, JM, Johengen, MJ, Hendricks-Munoz, K, Gerrets, R, Black, SM & Fineman, JR 2001, 'Inhaled nitric oxide-induced rebound pulmonary hypertension: Role for endothelin-1', American Journal of Physiology - Heart and Circulatory Physiology, vol. 280, no. 2 49-2.
Mcmullan DM, Bekker JM, Johengen MJ, Hendricks-Munoz K, Gerrets R, Black SM et al. Inhaled nitric oxide-induced rebound pulmonary hypertension: Role for endothelin-1. American Journal of Physiology - Heart and Circulatory Physiology. 2001 Feb 1;280(2 49-2).
Mcmullan, D. Michael ; Bekker, Janine M. ; Johengen, Michael J. ; Hendricks-Munoz, Kaken ; Gerrets, Rene ; Black, Stephen Matthew ; Fineman, Jeffrey R. / Inhaled nitric oxide-induced rebound pulmonary hypertension : Role for endothelin-1. In: American Journal of Physiology - Heart and Circulatory Physiology. 2001 ; Vol. 280, No. 2 49-2.
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