Inhibition of the Ca2+-sensing receptor rescues pulmonary hypertension in rats and mice

Qiang Guo, Jian An Huang, Aya Yamamura, Hisao Yamamura, Adriana M. Zimnicka, Ruby Fernandez, Jason X.J. Yuan

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

A recent study from our group demonstrated that the Ca2+-sensing receptor (CaSR) was upregulated, and the extracellular Ca2+-induced increase in cytosolic Ca2+ concentration (Ca2+ cyt) was enhanced in pulmonary arterial smooth muscle cells from patients with idiopathic pulmonary arterial hypertension and animals with experimental pulmonary hypertension (PH). However, it is unclear whether CaSR antagonists (for example, NPS2143) rescue the development of experimental PH. We tested the rescue effects of NPS2143 in rats with monocrotaline (MCT)-induced PH and mice with chronic hypoxia-induced PH. For the NPS2143 treatment group, rats and mice were i.p. injected with NPS2143 once per day from days 14 to 24. Four weeks after MCT injection or exposure to normobaric hypoxia, the right ventricular (RV) systolic pressure, right heart hypertrophy (RV/LV+S ratio) and RV myocardial fibrosis were rescued or nearly restored to normal levels by NPS2143 treatment. The rescue effects of NPS2143 on experimental PH further support a critical role for the CaSR in the PH mechanism. Therefore, NPS2143 may be a promising potential treatment for pulmonary arterial hypertension.

Original languageEnglish (US)
Pages (from-to)116-124
Number of pages9
JournalHypertension Research
Volume37
Issue number2
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Keywords

  • NPS2143
  • hypoxia
  • monocrotaline
  • mouse
  • rat

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Guo, Q., Huang, J. A., Yamamura, A., Yamamura, H., Zimnicka, A. M., Fernandez, R., & Yuan, J. X. J. (2014). Inhibition of the Ca2+-sensing receptor rescues pulmonary hypertension in rats and mice. Hypertension Research, 37(2), 116-124. https://doi.org/10.1038/hr.2013.129