m-Nisoldipine attenuates monocrotaline-induced pulmonary hypertension by suppressing 5-HT/ERK MAPK pathway.
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.
Chen
Xue-yan
XY
Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
Zhang
Wei
W
Miao
Qing-feng
QF
Zhang
Yong-jian
YJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000097:blood; D015737:Nisoldipine / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000097:blood
D000959:Antihypertensive Agents; D018809:Proliferating Cell Nuclear Antigen; D012701:Serotonin; D015737:Nisoldipine; D016686:Monocrotaline; D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases