Strathprints logo
Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

Acute hypoxia stimulates intracellular peroxynitrite formation associated with pulmonary artery smooth muscle cell proliferation

Agbani, Ejaife O. and Coats, Paul and Wadsworth, Roger M. (2011) Acute hypoxia stimulates intracellular peroxynitrite formation associated with pulmonary artery smooth muscle cell proliferation. Journal of Cardiovascular Pharmacology, 57 (5). pp. 584-588. ISSN 0160-2446

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

There is separate evidence for peroxynitrite formation and hypoxia-induced cell proliferation in several models of hypoxic pulmonary hypertension. We therefore hypothesized that the stimulation of pulmonary artery smooth muscle cells (PASMCs) proliferation by hypoxia is due to peroxynitrite formation. The effect of hypoxia alone and in combination with <0.2 mu M peroxynitrite on PASMCs was investigated in explants from bovine lungs grown in 1%, 5%, or 10% oxygen for 24 hours with or without peroxynitrite. At 0.1% fetal bovine serum, DNA synthesis of PASMCs (assessed by H-3 thymidine incorporation) was increased by transient exposure to 0.2 mu M peroxynitrite (by 158% +/- 14%, P < 0.01) or to 24 hours of hypoxia (5% oxygen) (by 221% +/- 17%, P < 0.01). Results were similar at 2.5% fetal bovine serum. Treatment of PASMCs with 0.2 mu M peroxynitrite or 5% O-2 hypoxia caused a significant increase in nitrotyrosine formation to a similar extent and intensity. The proliferative response to 0.2 mu M peroxynitrite or to the combination of peroxynitrite plus 5% O-2 was similar to the effect of 5% O-2 alone and was abolished by simultaneous treatment with peroxynitrite scavenger-ebselen (5 mu M). Our present data indicate that hypoxia can initiate peroxynitrite-induced proliferative events and suggest a mechanism for the vascular hypertrophy associated with pulmonary hypertension.

Item type: Article
ID code: 31490
Keywords: hypoxia, peroxynitrite, pulmonary hypertension, smooth muscle cells, hypertension, superoxide, ebselen, rats, GP91(PHOX), NOX4, Therapeutics. Pharmacology, Pharmacology, Cardiology and Cardiovascular Medicine
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
Depositing user: Pure Administrator
Date Deposited: 14 Jun 2011 14:30
Last modified: 27 Mar 2014 09:23
URI: http://strathprints.strath.ac.uk/id/eprint/31490

Actions (login required)

View Item