Back to Search
Start Over
Acute vasodilator effects of Rho-kinase inhibitors in neonatal rats with pulmonary hypertension unresponsive to nitric oxide.
- Source :
-
American Journal of Physiology: Lung Cellular & Molecular Physiology . Feb2008, Vol. 294, pL205-L213. 9p. 2 Diagrams, 1 Chart, 6 Graphs. - Publication Year :
- 2008
-
Abstract
- Pulmonary hypertension (PHT) in neonates is often refractory to the current best therapy, inhaled nitric oxide (NO). The utility of a new class of pulmonary vasodilators, Rho-kinase (ROCK) inhibitors, has not been examined in neonatal animals. Our objective was to examine the activity and expression of RhoA/ROCK in normal and injured pulmonary arteries and to determine the short-term pulmonary hemodynamic (assessed by pulse wave Doppler) effects of ROCK inhibitors (15 mg·kg-1 ip Y-27632 or 30 mg/kg ip fasudil) in two neonatal rat models of chronic PHT with pulmonary vascular remodeling (chronic hypoxia, 0.13 FIO2, or 1 mg·kg-1·day-1 ip chronic bleomycin for 14 days from birth). Activity of the RhoA/ROCK pathway and ROCK expression were increased in hypoxia- and bleomycin-induced PHT. In both models, severe PHT [characterized by raised pulmonary vascular resistance (PVR) and impaired right ventricular (RV) performance] did not respond acutely to inhaled NO (20 ppm for 15 mm) or to a single bolus of a NO donor, 3-morpholinosydnonimine hydrochloride (SIN-I; 2 µg/kg ip). In contrast, a single intraperitoneal bolus of either ROCK inhibitor (Y-27632 or fasudil) completely normalized PVR but had no acute effect on RV performance. ROCK-mediated vasoconstriction appears to play a key role in chronic PHT in our two neonatal rat models. Inhibitors of ROCK have potential as a testable therapy in neonates with PHT that is refractory to NO. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10400605
- Volume :
- 294
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Lung Cellular & Molecular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30014162
- Full Text :
- https://doi.org/10.1152/ajplung.00234.2007