Effect of Theophylline on Hypoxic Pulmonary Vasoconstriction in Awake Rats.

Arisaka, Yasusi; Sato, Shinobu; Kato, Shigeaki; Yuki, Hideki; Takahashi, Hifumi; Tomoike, Hitonobu

doi:10.1620/tjem.182.231

Cited by 1 publication

(1 citation statement)

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“…We also initially expected that treatment with theophylline of rats undergoing the run-to-fatigue protocol in hypobaric hypoxia would further augment pulmonary extracellular fluid content reflected by an increase of lung weight WDR. The observation that theophylline alone did not increase vascular leak might be explained by the known vasodilatory effects of theophylline and its reported ability to reduce HPV (5). Sitaxsentan, however, had the opposite effect, increasing the fraction of blood present in the pulmonary vasculature, which is reflected by the increased lung weight WDR after sitaxsentan treatment (Fig.…”

Section: Pulmonary Wdrmentioning

confidence: 90%

The combination of theophylline and endothelin receptor antagonism improves exercise performance of rats under simulated high altitude

Radiloff

Zhao

Boico

et al. 2012

Journal of Applied Physiology

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Decreased physical performance is a well-known consequence of rapid ascent to high altitude. Hypoxic pulmonary vasoconstriction (HPV) potentially limits cardiac output and systemic blood flow, thus preventing successful adaptation to rapid ascent. We hypothesized that pharmacological enhancement of the heart rate with theophylline, combined with reversal of HPV via endothelin blockade, could increase exercise performance at high altitude. Female Sprague-Dawley rats were treated with combinations of 1) theophylline, 2) the endothelin receptor antagonists sitaxsentan/ambrisentan, and/or 3) phosphodiesterase-5 inhibitor sildenafil and exposed to either a simulated high altitude (4,267 m) or 12% oxygen. Exercise capacity, peripheral blood flow, hemodynamics, and pulmonary leak were examined. Combination treatment with theophylline and endothelin blockade, but not with the respective single compounds, significantly prolonged run-to-fatigue time under simulated high altitude. No such efficacy was found when theophylline was combined with sildenafil. Neither theophylline nor sitaxsentan or their combination influenced breathing rates and hemoglobin oxygen saturation. Whereas under hypoxia, theophylline significantly increased muscular blood flow, and sitaxsentan increased tissue oxygenation, the combination improved both parameters but in a reduced manner. Under hypoxia, the combination treatment but not the single compounds significantly enhanced pulmonary arterial pressure compared with controls (13.1 ± 6.3 vs. 11.9 ± 5.2 mmHg), whereas mean arterial pressure remained unaffected. Pulmonary wet-to-dry weight ratios were unaffected by combination treatment. We conclude that concomitant dosing with a cardiac stimulant and endothelin antagonist can partially reverse loss of physical performance capacity under hypobaric hypoxia, independent from improving blood oxygen saturation.

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Section: Pulmonary Wdrmentioning

confidence: 90%