Role of endothelin ET B receptor in the pathogenesis of monocrotaline-induced pulmonary hypertension in rats

Masahiro Nishida, Yuka Okada, Kenji Akiyoshi, Keiko Eshiro, Masanori Takaoka, Cheryl E. Gariepy, Masashi Yanagisawa, Yasuo Matsumura

Research output: Contribution to journalArticle

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Abstract

We investigated the role of endothelin ET B receptor in the development of monocrotaline-induced pulmonary hypertension, by using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the endothelin ET B receptor gene. Three weeks after injection of saline or monocrotaline (60 mg/kg, s.c.), hemodynamics, cardiac hypertrophy and endothelin-1 levels in right ventricle were determined. Monocrotaline produced a marked pulmonary hypertension associated with increases in right ventricular pressure and hypertrophy, pulmonary arterial medial thickening and the endothelin-1 levels. These monocrotaline-induced alterations tended to be enhanced in ET B-deficient homozygous rats, compared with cases in wild-type rats. The treatment with the selective ET A receptor antagonist ABT-627 [2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n- butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid] for 3 weeks (10 mg/kg/day, twice daily) almost completely suppressed the monocrotaline-induced pulmonary hypertension and related organ damage both in ET B-deficient and wild-type animals to the same levels. Thus, we suggest that the antagonism of the ET A receptor is essential for the protection from monocrotaline-induced pulmonary hypertension, irrespective of the presence of the ET B receptors, although a protective role of ET B receptor-mediated action in the pathogenesis of this disease model cannot be ruled out.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalEuropean Journal of Pharmacology
Volume496
Issue number1-3
DOIs
StatePublished - Aug 2 2004

Fingerprint

Monocrotaline
Endothelin B Receptors
Pulmonary Hypertension
Endothelin-1
Right Ventricular Hypertrophy
Metrorrhagia
Wild Animals
Cardiomegaly
Ventricular Pressure
Heart Ventricles
Hemodynamics
Lung
Injections
Genes

Keywords

  • Endothlin-1
  • ET receptor
  • ET receptor
  • ET receptor-deficient rat
  • Monocrotaline
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Nishida, M., Okada, Y., Akiyoshi, K., Eshiro, K., Takaoka, M., Gariepy, C. E., ... Matsumura, Y. (2004). Role of endothelin ET B receptor in the pathogenesis of monocrotaline-induced pulmonary hypertension in rats. European Journal of Pharmacology, 496(1-3), 159-165. https://doi.org/10.1016/j.ejphar.2004.06.028

Role of endothelin ET B receptor in the pathogenesis of monocrotaline-induced pulmonary hypertension in rats. / Nishida, Masahiro; Okada, Yuka; Akiyoshi, Kenji; Eshiro, Keiko; Takaoka, Masanori; Gariepy, Cheryl E.; Yanagisawa, Masashi; Matsumura, Yasuo.

In: European Journal of Pharmacology, Vol. 496, No. 1-3, 02.08.2004, p. 159-165.

Research output: Contribution to journalArticle

Nishida, Masahiro ; Okada, Yuka ; Akiyoshi, Kenji ; Eshiro, Keiko ; Takaoka, Masanori ; Gariepy, Cheryl E. ; Yanagisawa, Masashi ; Matsumura, Yasuo. / Role of endothelin ET B receptor in the pathogenesis of monocrotaline-induced pulmonary hypertension in rats. In: European Journal of Pharmacology. 2004 ; Vol. 496, No. 1-3. pp. 159-165.
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