ZAPRINAST ATTENUATES HYPOXIC PULMONARY ARTERY INJURY AND CAUSES LESS AORTIC RELAXATION THAN MILRINONE
| Autor: | Paul R. Crisostomo, Jeffrey M. Pitcher, Daniel R. Meldrum, Ajay Kher, Meijing Wang, Ben M. Tsai |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Lung Diseases
Male medicine.medical_specialty Time Factors Purinones Phosphodiesterase Inhibitors Hypertension Pulmonary Vasodilator Agents Aorta Thoracic Pulmonary Artery Critical Care and Intensive Care Medicine Polymerase Chain Reaction Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Hypoxic pulmonary vasoconstriction medicine.artery medicine Animals Thoracic aorta RNA Messenger Hypoxia Lung Aorta Inflammation Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha business.industry Drug Synergism medicine.disease Pulmonary hypertension Rats chemistry Vasoconstriction Anesthesia Pulmonary artery Circulatory system Emergency Medicine Cardiology Milrinone business Zaprinast Interleukin-1 medicine.drug |
| Zdroj: | Shock. 24:417-420 |
| ISSN: | 1073-2322 |
| Popis: | Hypoxic pulmonary vasoconstriction is a challenging clinical problem with limited therapeutic options. Milrinone, a phosphodiesterase (PDE)-3 inhibitor, is frequently used to treat perioperative pulmonary hypertension. However, recent evidence suggests that the PDE-5 isoform may be more specific for lung tissue. We hypothesized that the PDE-5 inhibitor zaprinast has greater efficacy for pulmonary vasorelaxation, attenuation of hypoxic pulmonary vasoconstriction, and inhibition of hypoxia-induced pulmonary artery cytokine expression when compared with milrinone. To study this, isolated rat pulmonary artery and thoracic aorta rings suspended in physiologic organ baths for measurement of isometric force transduction were treated with vehicle (dimethyl sulfoxide), milrinone, or zaprinast to assess pulmonary artery relaxation, thoracic aorta relaxation, inhibition of hypoxic (pO2 = 30-35 mmHg) pulmonary vasoconstriction, and hypoxia-induced pulmonary artery TNF-alpha and IL-1beta expression (reverse transcriptase-PCR). Milrinone and zaprinast resulted in dose-dependent pulmonary artery and aortic relaxation, but zaprinast caused significantly less aortic relaxation compared with milrinone (50.12% +/- 3.36% versus 91.03% +/- 2.97%, P < 0.001). Zaprinast, but not milrinone, significantly inhibited hypoxic pulmonary vasoconstriction (zaprinast, 58.42% +/- 5.37%; milrinone, 77.65% +/- 4.42% versus vehicle: 74.42% +/- 7.54%). Hypoxia-induced upregulation of TNF-alpha and IL-1beta mRNA in pulmonary artery was decreased by zaprinast, but not milrinone, pretreatment. These results suggest that zaprinast, but not milrinone, preferentially vasodilates pulmonary artery over aorta, attenuates hypoxic pulmonary vasoconstriction, and inhibits hypoxia-induced pulmonary artery TNF-alpha and IL-1beta expression. Therefore, PDE-5 inhibition may be advantageous in the treatment of pulmonary hypertension. |
| Databáze: | OpenAIRE |
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