PMID- 1400001 OWN - NLM STAT- MEDLINE DCOM- 19921112 LR - 20171213 IS - 8750-7587 (Print) IS - 0161-7567 (Linking) VI - 73 IP - 2 DP - 1992 Aug TI - Acute and long-term TNF-alpha administration increases pulmonary vascular reactivity in isolated rat lungs. PG - 708-12 AB - Tumor necrosis factor-alpha (TNF-alpha) causes pulmonary hypertension and arterial hypoxemia, but the mechanisms are unknown. We conducted two experiments to test the hypothesis that TNF-alpha alters pulmonary vascular reactivity, which in turn could cause either pulmonary hypertension or arterial hypoxemia. In experiment 1, rats were given acute or long-term injections of TNF-alpha (recombinant human) in vivo. Rats treated acutely received either saline or TNF-alpha (40 micrograms/kg iv in saline) 3 min (TNF-3 min; n = 8), 20 min (TNF-20 min; n = 8), or 24 h (TNF-24 h; n = 5) before the lungs were isolated. Rats treated chronically received injections of either saline or TNF-alpha (250 micrograms/kg ip in saline) two times per day for 7 days (TNF-7 days; n = 9). Lungs were isolated and perfused with Earle's salt solution (+2 g/l NaHCO3 + 4 g/100 ml Ficoll), and vascular reactivity was tested with acute hypoxia (3 min; 3% O2) and angiotensin II (ANG II; 0.025-0.40 micrograms). Pulmonary pressor responses to hypoxia were greater (P less than 0.05) in TNF-20 min and TNF-7 day groups. ANG II responses were increased (P less than 0.05) in TNF-7 day rats. In experiment 2, lungs were isolated and perfused and received direct pulmonary arterial injections of TNF-alpha (0.2, 2.0, and 20 micrograms) or saline, after stable responses to hypoxia and ANG II (0.10 microgram) were attained. Reactivity was not different between control and TNF-alpha rats before the injections, but TNF-alpha increased (P less than 0.05) responses to hypoxia and ANG II.(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Stevens, T AU - Stevens T AD - Department of Physiology, Colorado State University, Fort Collins 80523. FAU - Janssen, P L AU - Janssen PL FAU - Tucker, A AU - Tucker A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Appl Physiol (1985) JT - Journal of applied physiology (Bethesda, Md. : 1985) JID - 8502536 RN - 0 (Tumor Necrosis Factor-alpha) RN - 11128-99-7 (Angiotensin II) SB - IM MH - Angiotensin II/pharmacology MH - Animals MH - Blood Pressure/drug effects MH - Female MH - Hematocrit MH - In Vitro Techniques MH - Lung/*drug effects MH - Organ Size/drug effects MH - Pulmonary Circulation/*drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1992/08/01 00:00 MHDA- 1992/08/01 00:01 CRDT- 1992/08/01 00:00 PHST- 1992/08/01 00:00 [pubmed] PHST- 1992/08/01 00:01 [medline] PHST- 1992/08/01 00:00 [entrez] AID - 10.1152/jappl.1992.73.2.708 [doi] PST - ppublish SO - J Appl Physiol (1985). 1992 Aug;73(2):708-12. doi: 10.1152/jappl.1992.73.2.708.