m-Nisoldipine attenuates monocrotaline-induced pulmonary hypertension by suppressing 5-HT/ERK MAPK pathway

Xue-yan Chen1, Wei Zhang, Qing-feng Miao

  • 1Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.

Insights

New drug m-nisoldipine (m-Nis) effectively treats pulmonary hypertension (PH) in rats by reducing pulmonary artery pressure and remodeling. It works by lowering 5-HT levels and inhibiting the ERK/MAPK pathway.

Area of Science:

  • Pharmacology
  • Cardiovascular Research
  • Cell Biology

Background:

  • Pulmonary hypertension (PH) is a severe condition characterized by elevated pulmonary artery pressure.
  • Monocrotaline (MCT) injection is a common method to induce PH in animal models for research.
  • Investigating novel therapeutic agents for PH is crucial.

Purpose of the Study:

  • To evaluate the efficacy of a new calcium antagonist, m-nisoldipine (m-Nis), in treating MCT-induced PH in rats.
  • To elucidate the underlying mechanisms by which m-Nis exerts its protective effects against PH.

Main Methods:

  • Rats were induced with PH using a single subcutaneous injection of MCT.
  • Pulmonary hemodynamics and lung tissue morphology were assessed.
  • Biochemical markers (MDA, SOD) and protein expressions (PCNA, ERK1, p-ERK, 5-HT) were analyzed using serum tests, Western blotting, and immunohistochemistry.

Main Results:

  • MCT-induced PH rats showed elevated pulmonary artery pressure (PAP), right ventricular index, and pulmonary artery muscularization, which were significantly attenuated by m-Nis treatment.
  • m-Nis treatment led to reduced MDA production and increased SOD activity in serum.
  • m-Nis significantly decreased the proliferation of PCNA and 5-HT positive smooth muscle cells and suppressed the p-ERK/ERK1 ratio in pulmonary arteries.

Conclusions:

  • M-nisoldipine demonstrates protective effects against MCT-induced pulmonary hypertension in rats.
  • The therapeutic benefits of m-Nis are associated with decreased PAP, right ventricular index, pulmonary artery remodeling, and smooth muscle cell proliferation.
  • These effects may be mediated through the reduction of 5-HT and the inhibition of the ERK/MAPK signaling pathway.

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