Adrenergic mechanisms in infection. III. alpha-and beta-receptor blocking agents in treatment.
Raised epinephrine concentrations concentrations developed in the blood of mice near death after an intraperitoneal challenge with 10(9) Staphylococcus aureus or Escherichia coli. Both epinephrine levels were elevated in the urine near death. These challenges were infections and not intoxications, as they could be successfully treated with antibiotics. Using the same model infections, we studied the effect of alpha-and beta-receptor blocking agents and other adrenergically active compounds. The compounds alone were not toxic in the doses used. alpha-Blockers, such as phenoxybenzamine, dibenamine, and ergotamine and beta-blockers, such as butoxamine, timolol, and practolol, were ineffective. Phentolamine alone or propranolol alone showed some evidence of an ability to prolong life in S. aureus infections. Together they lengthened life significantly in S. aureus-challenged mice. In E. coli infections this beneficial effect was not noted. Mice pretreated with reserpine (7 mg/kg) and challenged with S. aureus lived 55% longer than saline-treated controls. Less benefit was noted in E. coli infections. Serontonin treatment was helpful in S. aureus infections and deleterious in E. coli infections.
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D012701:Serotonin / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality; D013329:Structure-Activity Relationship
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D012701:Serotonin