bn-50730 and Hypotension

bn-50730 has been researched along with Hypotension* in 1 studies

Other Studies

1 other study(ies) available for bn-50730 and Hypotension

Article	Year
Dissociation of TNF-alpha from endotoxin-induced nitric oxide and acute-phase hypotension. The American journal of physiology, 1997, Volume: 273, Issue:1 Pt 2 We tested the concept that tumor necrosis factor-alpha (TNF-alpha) or platelet-activating factor (PAF) mediated Escherichia coli endotoxin lipopolysaccharide (LPS)-induced upregulation of nitric oxide (NO) and acute-phase hypotension (APH) in the rat. LPS (0.5 mg/kg i.v.) given to rats treated with saline or nonimmune goat-derived gamma-globulin (immunoglobulin G, 22 mg/kg i.m.) produced APH and increased plasma concentrations of TNF-alpha and nitrate and nitrite anions (reactive nitrogen intermediates; RNI) and NO in ex vivo incubates of polymorphonuclear neutrophils (PMN) and inducible NO synthase (iNOS) mRNA in PMN. Pretreatment of rats with a polyclonal TNF-alpha antibody (TNF-Ab, 22 mg/kg i.m.) abolished LPS-mediated increases in plasma TNF-alpha but failed to inhibit APH or the NO system. TNF-alpha (8.2 micrograms/kg i.v.) produced transient hypertension and sustained tachycardia and increased plasma TNF-alpha and PMN iNOS mRNA but not RNI. LPS and TNF-alpha decreased spontaneous and calcimycin (Ca2+ ionophore, 1 microM)- and PAF (1 microM)-mediated increases in head-space NO production by rings of mesenteric artery incubated ex vivo. TNF-Ab abolished all effects of TNF-alpha. PAF (25, 50, and 100 ng/kg) produced APH without increasing plasma TNF-alpha, RNI, or PMN iNOS mRNA. The PAF receptor antagonist BN-50730 (80 micrograms/kg i.v.) abolished PAF-induced APH and attenuated LPS-induced increases in RNI. We conclude that 1) LPS produces parallel but unrelated changes in TNF-alpha and RNI in plasma and PMN during the APH of endotoxemia; and 2) endogenous TNF-alpha is not required for LPS-mediated induction of iNOS mRNA, and PAF mediates LPS-induced APH. Topics: Animals; Azepines; Blood Pressure; Endotoxins; Enzyme Induction; Escherichia coli; Heart Rate; Hypotension; Immunoglobulin G; Lipopolysaccharides; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; Neutrophils; Nitric Oxide; Nitric Oxide Synthase; Platelet Activating Factor; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thienopyridines; Time Factors; Transcription, Genetic; Triazoles; Tumor Necrosis Factor-alpha	1997

Article

Year

Dissociation of TNF-alpha from endotoxin-induced nitric oxide and acute-phase hypotension.

The American journal of physiology, 1997, Volume: 273, Issue:1 Pt 2

We tested the concept that tumor necrosis factor-alpha (TNF-alpha) or platelet-activating factor (PAF) mediated Escherichia coli endotoxin lipopolysaccharide (LPS)-induced upregulation of nitric oxide (NO) and acute-phase hypotension (APH) in the rat. LPS (0.5 mg/kg i.v.) given to rats treated with saline or nonimmune goat-derived gamma-globulin (immunoglobulin G, 22 mg/kg i.m.) produced APH and increased plasma concentrations of TNF-alpha and nitrate and nitrite anions (reactive nitrogen intermediates; RNI) and NO in ex vivo incubates of polymorphonuclear neutrophils (PMN) and inducible NO synthase (iNOS) mRNA in PMN. Pretreatment of rats with a polyclonal TNF-alpha antibody (TNF-Ab, 22 mg/kg i.m.) abolished LPS-mediated increases in plasma TNF-alpha but failed to inhibit APH or the NO system. TNF-alpha (8.2 micrograms/kg i.v.) produced transient hypertension and sustained tachycardia and increased plasma TNF-alpha and PMN iNOS mRNA but not RNI. LPS and TNF-alpha decreased spontaneous and calcimycin (Ca2+ ionophore, 1 microM)- and PAF (1 microM)-mediated increases in head-space NO production by rings of mesenteric artery incubated ex vivo. TNF-Ab abolished all effects of TNF-alpha. PAF (25, 50, and 100 ng/kg) produced APH without increasing plasma TNF-alpha, RNI, or PMN iNOS mRNA. The PAF receptor antagonist BN-50730 (80 micrograms/kg i.v.) abolished PAF-induced APH and attenuated LPS-induced increases in RNI. We conclude that 1) LPS produces parallel but unrelated changes in TNF-alpha and RNI in plasma and PMN during the APH of endotoxemia; and 2) endogenous TNF-alpha is not required for LPS-mediated induction of iNOS mRNA, and PAF mediates LPS-induced APH.

Topics: Animals; Azepines; Blood Pressure; Endotoxins; Enzyme Induction; Escherichia coli; Heart Rate; Hypotension; Immunoglobulin G; Lipopolysaccharides; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; Neutrophils; Nitric Oxide; Nitric Oxide Synthase; Platelet Activating Factor; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thienopyridines; Time Factors; Transcription, Genetic; Triazoles; Tumor Necrosis Factor-alpha

1997