Nitric oxide-dependent pulmonary vasodilation in polycythemic rats.
Polycythemia causes increased vascular production of nitric oxide (NO), most likely secondary to an effect of elevated vascular shear stress to enhance expression of endothelial nitric oxide synthase (eNOS). Because both polycythemia and increased eNOS expression are associated with chronic hypoxia-induced pulmonary hypertension, experiments were performed to test the hypothesis that increased hematocrit leads to upregulation of pulmonary eNOS and enhanced vascular production of NO independent of hypoxia. Rats were administered human recombinant erythropoietin (rEpo; 48 U/day) or vehicle for 2 wk. At the time of study, hematocrit was significantly greater in the rEpo-treated group than in the vehicle group (65.8 +/- 0.7% vs. 45.1 +/- 0.5%), although mean pulmonary artery pressure did not differ between treatments. Experiments on isolated, saline-perfused lungs demonstrated similar vasodilatory responses to the endothelium-derived NO-dependent agonist ionomycin in each group. Additional experiments showed that the vasoconstrictor response to the thromboxane mimetic U-46619 was diminished at lower doses in lungs from the rEpo group compared with the vehicle group. However, perfusate nitrite/nitrate concentration after 90 min of perfusion in isolated lungs was not different between groups. Additionally, no difference was detected between groups in lung eNOS levels by Western blot. We conclude that the predicted increase in shear stress associated with polycythemia does not result in altered pulmonary eNOS expression.
Walker
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BR
Vascular Physiology Group, Departments of Cell Biology and Physiology and Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA. bwalker@salud.unm.edu
Resta
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Nelin
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004921:Erythropoietin; D006400:Hematocrit; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000737:chemistry / Q000187:drug effects; D008297:Male; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000032:analysis; D011086:Polycythemia / Q000139:chemically induced / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D007476:Ionophores; D009566:Nitrates; D009573:Nitrites; D011994:Recombinant Proteins; D014662:Vasoconstrictor Agents; D004921:Erythropoietin; D009569:Nitric Oxide; D015759:Ionomycin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat