Related Experiment Video
Updated: Jun 26, 2026

The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
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.
Abstract:
Effect of new calcium antagonist m-nisoldipine (m-Nis) on MCT-induced PH in rats and its mechanisms were investigated. Rats were injected with a single dose (60 mg x kg(-1)) of MCT subcutaneously to induce PH. Pulmonary haemodynamic measurement and lung tissue morphological investigations were undertaken. The MDA production and SOD activity in the serum were tested. PCNA, ERK1 and p-ERK expressions were analyzed by Western blotting. The expressions of 5-HT and PCNA were observed with immunohistochemistry. Results suggested that the PAP, right ventricular index and the degree of muscularization of small pulmonary artery were elevated markedly in MCT group, which was attenuated by m-Nis treatment. A significant reduction in MDA production and an increase in the SOD activity in the serum were also observed in all three m-Nis groups. The number of PCNA and 5-HT positive smooth muscle cells increased significantly in MCT group, and m-Nis treatment attenuated the expression obviously. Western blotting results suggested that the protein expression of PCNA and the ratio of p-ERK/ ERK1 increased markedly in MCT group and decreased by m-Nis. In conclusion, m-Nis protected against MCT-induced PH by decreasing PAP, right ventricular index, PAMSCs proliferation and pulmonary artery remodelling, which may be related to the reduction of 5-HT and the suppression of the ERK/MAPK signal pathway.
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.
Related Concept Videos
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
Antihypertensive Drugs: Vasodilators
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Nitric Oxide Signaling Pathway