NO causes perinatal pulmonary vasodilation through K+-channel activation and intracellular Ca2+release
| Autor: | David N. Cornfield, Robert B. Miller, Carlos Milla, Connie B Saqueton, Valerie A. Porter |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pulmonary Circulation medicine.medical_specialty Potassium Channels Physiology Vasodilation Nitric Oxide Nitric oxide chemistry.chemical_compound Fetus Physiology (medical) Internal medicine medicine.artery Potassium Channel Blockers medicine Animals Enzyme Inhibitors Sheep Ryanodine business.industry Phosphotransferases Intracellular Membranes Cell Biology Calcium Channel Blockers medicine.disease Pulmonary hypertension Potassium channel medicine.anatomical_structure Endocrinology chemistry Anesthesia Circulatory system Pulmonary artery Calcium Nucleotides Cyclic business Intracellular Blood vessel |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 276:L925-L932 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | Evidence suggests that nitric oxide (NO) causes perinatal pulmonary vasodilation through K+-channel activation. We hypothesized that this effect worked through cGMP-dependent kinase-mediated activation of Ca2+-activated K+channel that requires release of intracellular Ca2+from a ryanodine-sensitive store. We studied the effects of 1) K+-channel blockade with tetraethylammonium, 4-aminopyridine, a voltage-dependent K+-channel blocker, or glibenclamide, an ATP-sensitive K+-channel blocker; 2) cyclic nucleotide-sensitive kinase blockade with either KT-5823, a guanylate-sensitive kinase blocker, or H-89, an adenylate-sensitive kinase blocker; and 3) blockade of intracellular Ca2+release with ryanodine on NO-induced pulmonary vasodilation in acutely prepared late-gestation fetal lambs. N-nitro-l-arginine, a competitive inhibitor of endothelium-derived NO synthase, was infused into the left pulmonary artery, and tracheotomy was placed. The animals were ventilated with 100% oxygen for 20 min, followed by ventilation with 100% oxygen and inhaled NO at 20 parts/million (ppm) for 20 min. This represents the control period. In separate protocols, the animals received an intrapulmonary infusion of the different blockers and were ventilated as above. Tetraethylammonium ( n = 6 animals) and KT-5823 ( n = 4 animals) attenuated the response, whereas ryanodine ( n = 5 animals) blocked NO-induced perinatal pulmonary vasodilation. 4-Aminopyridine ( n = 5 animals), glibenclamide ( n = 5 animals), and H-89 ( n = 4 animals) did not affect NO-induced pulmonary vasodilation. We conclude that NO causes perinatal pulmonary vasodilation through cGMP-dependent kinase-mediated activation of Ca2+-activated K+channels and release of Ca2+from ryanodine-sensitive stores. |
| Databáze: | OpenAIRE |
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