Search

AbstractPapamatheakis, 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爖ꞝ, nonselective cation channels (NSCC), and reverse-mode sodium-Ca2笗Ⅺ砞. 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-HT2Aantagonist, shifted the 5-HT potency to a far greater extent than 1 μMGR-55562, a 5-HT1B/Dinhibitor. These influences were unaffected by LTH. The rank order for reducing 5-HT-induced PA contraction in normoxic animals was extracellular calcium removal≈10 mMNi2≈10 μMverapamil≈10 μMnifedipine with 50 μMSKF 96365>30 μMKB-R7943≈100 μMflufenamic acid≈10 μMnifedipine≈100 μMGd3> 100 μMLa3>500 μMNi2≈10 μMdiltiazem≈50 μM2-APB≈100 μMLOE 908. Contraction was not reduced by 100 μMspermine or 30 μMSN-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-HT2Aand 5HT1B/Dfunctions 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. [ABSTRACT FROM AUTHOR]