Preservation of Serotonin-Mediated Contractility in Adult Sheep Pulmonary Arteries Following Long-Term High-Altitude Hypoxia
| Autor: | Sean M. Wilson, Lawrence D. Longo, Srilakshmi Vemulakonda, Antoinette Dawson, Arlin B. Blood, William J. Pearce, Kurt Vrancken, Noah Osman, Quintin Blood, Monica Rubalcava, Allison Bennett, Demosthenes G. Papamatheakis, Ravi Goyal |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Serotonin
Scientific Articles medicine.medical_specialty Time Factors Calcium Channels L-Type Pyridines Physiology TRPM Cation Channels chemistry.chemical_element Altitude Sickness In Vitro Techniques Pulmonary Artery Serotonin 5-HT1 Receptor Antagonists Calcium Muscle Smooth Vascular Sodium-Calcium Exchanger Contractility Calcium imaging Nickel Internal medicine medicine.artery medicine Animals TRPC Cation Channels Microscopy Confocal Sheep Sodium-calcium exchanger Electrical impedance myography business.industry Myography Public Health Environmental and Occupational Health General Medicine Hypoxia (medical) Calcium Channel Blockers medicine.disease Pulmonary hypertension Endocrinology chemistry Benzamides Pulmonary artery Serotonin 5-HT2 Receptor Antagonists Female Spermine Ketanserin medicine.symptom business Muscle Contraction |
| Zdroj: | High Altitude Medicine & Biology. 12:253-264 |
| ISSN: | 1557-8682 1527-0297 |
| Popis: | Papamatheakis, Demostehens G., SrilakshmiVemulakonda, Quintin Blood, Ravi Goyal, Monica Rubalcava, Kurt Vrancken, Allison Bennett, Antoinette Dawson, Noah J. Osman, Arlin B. Blood, William J. Pearce, Lawrence D. Longo, and Sean M. Wilson. Preservation of serotonin-mediated contractility in adult sheep pulmonary arteries following long-term high-altitude hypoxia. High Alt. Med. Biol. 12:253–264.—Long-term hypoxia (LTH) can increase serotonin (5-HT) signaling as well as extracellular calcium entry in adult rodent pulmonary arteries (PA), and 5-HT is associated with pulmonary hypertension. Because LTH, 5-HT, and calcium entry are related, we tested the hypothesis that LTH increases 5-HT-mediated PA contractility and associated calcium influx through L-type Ca2+ channels, nonselective cation channels (NSCC), and reverse-mode sodium-Ca2+ exchange. We performed wire myography and confocal calcium imaging on pulmonary arteries from adult ewes that lived near sea level or were maintained at high-altitude (3801 m) for ∼110 days. LTH did not increase the arterial medial wall thickness, nor did it affect the potency or efficacy for 5-HT-induced PA contraction. Ketanserin (100 nM), a 5-HT2A antagonist, shifted the 5-HT potency to a far greater extent than 1 μM GR-55562, a 5-HT1B/D inhibitor. These influences were unaffected by LTH. The rank order for reducing 5-HT-induced PA contraction in normoxic animals was extracellular calcium removal≈10 mM Ni2+≈10 μM verapamil≈10 μM nifedipine with 50 μM SKF 96365>30 μM KB-R7943≈100 μM flufenamic acid≈10 μM nifedipine≈100 μM Gd3+> 100 μM La3+>500 μM Ni2+≈10 μM diltiazem≈50 μM 2-APB≈100 μM LOE 908. Contraction was not reduced by 100 μM spermine or 30 μM SN-6. LTH increased the effects of KB-R7943 and mitigated those of nifedipine but did not affect calcium responses in imaging studies. Overall, in adult sheep, arterial structure and 5-HT2A and 5HT1B/D functions are preserved following LTH while the role of NSCC-related calcium-dependent contraction is increased. These elements indicate preservation of PA contractility in LTH with minimal functional changes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|