Abstract | OBJECTIVE: DESIGN: Prospective, randomized, unblinded study. SETTING: Hospital research laboratory. SUBJECTS: Newborn Yorkshire-Landrace piglets. INTERVENTIONS: Normoxic animals were 3-6 days old. Hypoxic animals were exposed to hypoxia (Fio2 0.10) between 1 and 15 days of age to induce pulmonary hypertension and then were studied. MEASUREMENTS AND MAIN RESULTS: In isolated perfused lungs from normoxic piglets, we measured the perfusion pressure to assess the vasoconstrictor response to protein kinase C activation with phorbol 12,13-dibutyrate or 1-oleyl-2-acetyl-glycerol. We also assessed the effect of protein kinase C inhibition with staurosporine (2 x 10-6M) and chelerythrine (5 x 10-5M) on endothelin-1-induced pulmonary vasoconstriction. We then examined the effect of chelerythrine and phosphatase inhibition with phenylarsine oxide on the baseline perfusion pressure of normoxic and chronically hypoxic piglets. Phorbol 12,13-dibutyrate and 1-oleyl-2-acetyl-glycerol caused a sustained, dose-dependent increase in perfusion pressure, with relative potencies about 100- and 1000-fold less than endothelin-1, respectively. Protein kinase C inhibitors, chelerythrine and staurosporine, decreased the constrictor response to endothelin-1. Chelerythrine did not affect baseline perfusion pressure in the normoxic animal, whereas it lowered pulmonary vascular tone in chronically hypoxic animals. With respect to phosphatases, phenylarsine oxide significantly increased perfusion pressure in normoxia as well as in hypoxia. CONCLUSIONS: These findings confirm that protein kinase C activation causes sustained vasoconstriction in the neonatal pulmonary vasculature and mediates the vasoconstrictor action of potent peptides, like endothelin-1. These findings also confirm that protein kinase C activation could be induced by hypoxic exposure in the neonatal piglet pulmonary vasculature. Phosphatases appear to modulate pulmonary vascular tone in the normoxic and hypoxic newborn piglet.
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Authors | J W Berkenbosch, J Baribeau, E Ferretti, T Perreault |
Journal | Critical care medicine
(Crit Care Med)
Vol. 29
Issue 6
Pg. 1229-33
(Jun 2001)
ISSN: 0090-3493 [Print] United States |
PMID | 11395610
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
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Chemical References |
- Enzyme Inhibitors
- Protein Kinase C
- Phosphoric Monoester Hydrolases
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Topics |
- Analysis of Variance
- Animals
- Animals, Newborn
- Enzyme Inhibitors
(pharmacology)
- Hypertension, Pulmonary
(physiopathology)
- Hypoxia
(physiopathology)
- Phosphoric Monoester Hydrolases
(physiology)
- Prospective Studies
- Protein Kinase C
(physiology)
- Pulmonary Circulation
(drug effects)
- Signal Transduction
- Swine
- Vasoconstriction
(drug effects)
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