title: Protective action of amlodipine on cardiac negative inotropism induced by lipopolysaccharide in rats.
abstract: Amlodipine has been shown to prevent decrease in vascular responsiveness induced by injection of Salmonella typhosa lipopolysaccharide (LPS); however, there is no study reporting if this protection by amlodipine extends to ventricular contractility. Therefore, we have investigated in rat isolated right ventricle strips contracted by electrical stimulation (1 and 3 Hz and subsequently 1 Hz) whether pre-treatment with amlodipine (15 mg/kg orally for 1 week) precludes the decrease in ventricular contractility related to the induction of nitric oxide synthase stimulated by LPS injection (4 mg/kg intraperitoneally). The induction of septic shock was confirmed in isolated aortic rings from LPS-injected rats by verifying that the contractile response to 1 microM noradrenaline had been (i) decreased after LPS injection and (ii) markedly potentiated by the addition of 10 microM l-arginine. The injection of saline to untreated and amlodipine-treated rats produced a non-significant effect on right ventricular contractility during 180 min. at 3 Hz; the recovery of the contractile response was improved when the stimulation frequency was subsequently returned to 1 Hz after 30 min. In contrast, injection of LPS to untreated and amlodipine-treated rats (amlodipine + LPS) produced a decrease in right ventricular contractility during 180 min. at 3 Hz, an effect that was more pronounced in LPS than in amlodipine-treated rats. These ex vivo results obtained after LPS injection suggest that amlodipine may have inhibited, at least in part, the induction of nitric oxide synthase with a resulting preclusion of the cardiovascular failure produced by septic shock.
authors: Department of Pharmacobiology, Centro de Investigación y de Estudios Avanzados IPN, México D.F., México. gbravof@yahoo.com
authors: Guadalupe
authors: G
authors: Bravo
authors: Alexander
authors: A
authors: Kurtansky
authors: Francisco Javier
authors: FJ
authors: López-Muñoz
authors: Enrique
authors: E
authors: Hong
authors: Guillermo
authors: G
authors: Rojas
authors: Carlos M
authors: CM
authors: Villalón
authors: Fengyang
authors: F
authors: Huang
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001120:Arginine / Q000494:pharmacology; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000276:immunology; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D008070:Lipopolysaccharides; D020011:Protective Agents; D017311:Amlodipine; D001120:Arginine; D009638:Norepinephrine