Diminished pressor response to exogenous norepinephrine and angiotensin II in septic, unanesthetized rats: evidence for a prostaglandin-mediated effect.
Despite elevated plasma concentrations of norepinephrine (NE), septic patients generally have normal or low mean arterial pressure (MAP) and systemic vascular resistance. We tested the hypothesis that sustained sepsis in rats results in relative hyporesponsiveness to the pressor actions of NE and angiotensin II (AII). Sprague-Dawley rats were studied 48 hr after sepsis was induced by cecal ligation. Sham-operated rats served as controls. Carotid artery and jugular venous catheters were placed under halothane anesthesia and the rats were allowed to waken fully in restraining cages. Peak increments in MAP were measured after bolus iv doses of NE (0.125-8.0 micrograms/kg) or AII (0.0125-0.5 microgram/kg). Some rats were pretreated with indomethacin (5 mg/kg, iv) 30 min prior to the dose-response study. Data were fitted to a two-parameter hyperbolic function and the resulting curves were compared by analysis of variance. Compared with controls, sepsis decreased the pressor response to both NE (P less than 0.0001) and AII (P less than 0.0001). Indomethacin restored responsiveness toward normal for both pressor agents (P less than 0.0001). It is concluded that sepsis is associated with hyporesponsiveness to two chemically dissimilar vasopressors and that this phenomenon may be mediated by prostaglandins.
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000097:blood; D011464:Epoprostenol / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D011458:Prostaglandins E / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000097:blood / Q000503:physiopathology*
D004573:Electrolytes; D011458:Prostaglandins E; D000804:Angiotensin II; D011464:Epoprostenol; D010100:Oxygen; D009638:Norepinephrine; D007213:Indomethacin