Nitric oxide-dependent pulmonary vasodilation in polycythemic rats

Polycythemia causes increased vascular production of nitric oxide (NO), mos t likely secondary to an effect of elevated vascular shear stress to enhanc e expression of endothelial nitric oxide synthase (eNOS). Because both poly cythemia and increased eNOS expression are associated with chronic hypoxia- induced pulmonary hypertension, experiments were performed to test the hypo thesis that increased hematocrit leads to upregulation of pulmonary eNOS an d enhanced vascular production of NO independent of hypoxia. Rats were admi nistered 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 vasodi latory responses to the endothelium-derived NO-dependent agonist ionomycin in each group. Additional experiments showed that the vasoconstrictor respo nse to the thromboxane mimetic U-46619 was diminished at lower doses in lun gs from the rEpo group compared with the vehicle group. However, perfusate nitrite/nitrate concentration after 90 min of perfusion in isolated lungs w as not different between groups. Additionally, no difference was detected b etween groups in lung eNOS levels by Western blot. We conclude that the pre dicted increase in shear stress associated with polycythemia does not resul t in altered pulmonary eNOS expression.