Interferon-alpha elevates pulmonary blood pressure in sheep--the role of thromboxane cascade.
We tested the effect of interferon-alpha on lung function to examine whether interferon-alpha causes some pathophysiological change in the lung. We prepared awake sheep with chronic lung lymph fistula, and measured the pulmonary hemodynamics, lung fluid balance and concentrations of prostanoid products. At 1 h after intravenous interferon-alpha administration (18 x 10(6) I.U.), pulmonary arterial pressure and pulmonary vascular resistance were significantly increased compared to the baseline values. The levels of thromboxane B2 in both plasma and lung lymph were increased concomitant with early elevation on pulmonary arterial pressure. In addition, OKY-046 [sodium-3[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid] (10 mg kg(-1)), a selective thromboxane synthase inhibitor, significantly prevented the interferon-alpha-induced pulmonary hypertension and thromboxane B2 production. While no evidence of increased pulmonary vascular leakage was observed. These findings suggest that a single infusion of interferon-alpha stimulates a thromboxane cascade and causes transient pulmonary hypertension. However, interferon-alpha itself or increased thromboxane A2 might not affect the pulmonary vascular permeability in sheep.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000517:prevention & control; D007262:Infusions, Intravenous; D016898:Interferon-alpha / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008689:Methacrylates / Q000627:therapeutic use; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors