Vasoactive mediators in experimentally induced pulmonary hypertension in rats

P. Vijay, L. Szekely, T. G. Sharp, J. W. Brown

Research output: Contribution to journalArticle


Pulmonary hypertension (PH) leads to progressive elevation of pulmonary artery pressure resulting in right ventricle failure and death. Injury to pulmonary vasculature could lead to an imbalance in the levels of vasoactive mediators such as endothelin-1(ET-1) and nitric oxide (NO). The dynamic changes in these mediators, and also in adrenomedullin (ADM), a potent vasodilator/ peptide, were studied in rats. In order to understand the release of these mediators and postulate a mechanism of action, we induced PH in 250-300gm-Spraque Dawley rats (n=5) with a single dose of 60mg/kg b wt monocrotaline (MCT) given subcutaneously. Control rats (n=6) received the solvent alone. Six rats were pretreated with 3nmol ADM. After 3 weeks, blood levels ET-1, NO, ADM, cGMP, and cAMP were measured. The results are given in the following table. Control (n=6) MCT (n=5) ADM (n=6) ET-1(ng/ml) 0.32 ± 0.1 2.27 ± 0.3 0.46 ± 0.2 NO (μM) 3.95 ± 0.8 8.9 ± 2.1 3.87 ± 1.7 ADM (pg/ml) 5.4 ± 1.7 9.5 ± 2.4 11.5 ± 2.2 cGMP (pmol/ml) 8.72 ± 4 18.9 ± 3.8 10.4 ± 7.3 cAMP (pmol/ml) 0.02 ± 0.01 0.87 ± 0.45 0.07 ± 0.04 Results indicate that PH is induced by MCT as seen by significantly higher ET-1 levels compared to the controls (0.32 ± 0.1 vs 2.27 ± 0.3, p=0.0001). Persistent presence of MCT can damage pulmonary endothelial cells resulting in PH in spite of release of high levels of blood NO and ADM to compensate for the increase in pressure. Second messenger levels in ADM pretreated rats suggest that ADM may be mediating its effect via cAMP derived directly from endothelial and cGMP derived indirectly from the adjacent smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)120A
JournalJournal of Investigative Medicine
Issue number2
StatePublished - Feb 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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