title: Fludrocortisone and hydrocortisone, alone or in combination, on in vivo hemodynamics and in vitro vascular reactivity in normal and endotoxemic rats: a randomized factorial design study.
abstract: Hydrocortisone enhances the pressor response to catecholamines in healthy volunteers and septic shock patients. Similar data do not exist for fludrocortisone. We assessed the effects of single administrations of fludrocortisone and hydrocortisone on systolic blood pressure until 2 hours after treatments injection and on in vitro vascular contraction of mesenteric artery rings to phenylephrine at 3 hours, in normal and endotoxemic rats. Intravenous fludrocortisone (5 and 20 μg/kg) and hydrocortisone (4 and 20 mg/kg) were administered in 16 groups (8 without and 8 with lipopolysaccharide-induced endotoxemic shock) of 10 Wistar rats according to four 2 × 2-factorial designs. Fludrocortisone and hydrocortisone similarly increased systolic blood pressure (P < 0.001 for both) but more in endotoxemic than in normal animals. Fludrocortisone and hydrocortisone significantly modified contractile response to phenylephrine (P = 0.039 and P = 0.007, respectively). At dose 1, fludrocortisone had no effect and hydrocortisone decreased contraction, whereas, at dose 2, both fludrocortisone and hydrocortisone increased contraction, especially in endotoxemic rats and with additive effect. Our results show that single intravenous administrations of fludrocortisone and hydrocortisone increase blood pressure and contractile response of mesenteric arteries to phenylephrine. The magnitude of these effects depends on dose and pathophysiological conditions and is higher in endotoxemic than in normal rats.
authors.affiliation: *Inserm, CIC-P 0203 Clinical Investigation Centre, Rennes, France; †Experimental and Clinical Pharmacology Laboratory, University of Rennes 1, Rennes, France; and Departments of ‡Clinical Pharmacology; §Surgical Intensive Care; and ¶Hormonology, Rennes University Hospital, Rennes, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Laviolle
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nesseler
authors.forename: Catherine
authors.initials: C
authors.lastname: Massart
authors.forename: Eric
authors.initials: E
authors.lastname: Bellissant
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology; D005438:Fludrocortisone / Q000008:administration & dosage*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006854:Hydrocortisone / Q000008:administration & dosage*; D008297:Male; D009924:Organ Culture Techniques; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D005438:Fludrocortisone; D006854:Hydrocortisone