Protective action of amlodipine on cardiac negative inotropism induced by lipopolysaccharide in rats

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.