Endothelin-1 and nitric oxide mediated the lipopolysaccharide-induced cardiac negative inotropic role.
- Author:
Hui YAO
1
;
Jie TU
;
Qi-xian SHAN
;
Qiang XIA
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Depression, Chemical; Endothelin-1; physiology; Lipopolysaccharides; toxicity; Male; Myocardial Contraction; drug effects; physiology; Nitric Oxide; physiology; Rats; Rats, Sprague-Dawley; Shock, Septic; chemically induced; physiopathology
- From: Chinese Journal of Applied Physiology 2009;25(2):228-232
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) on lipopolysaccharide(LPS)-induced myocardial dysfunction, and explore the related underlying mechanisms.
METHODSExperimental septic model was established by intraperitoneal injection of LPS (10 mg x kg(-1)). The study was carried out on the isolated rat hearts to determine the roles of ET-1 and NO in the effect of LPS on the cardiac contractility and on the isolated rat ventricular myocytes model to observe the [Ca2+]i homeostasis in cardiac myocytes.
RESULTS(1) The levels of serum NO2-/NO3- and plasma ET-1 were markedly increased by LPS treatment for 4 hours. (2) LPS induced the decrease in rate-pressure product (RPP), and increase in left ventricular end-diastolic pressure (LVEDP) in the isolated perfused rat hearts. Pretreatment with either aminoguanidine (AMG) (100 mg x kg(-1), i.p.) or BQ-123 (1 mg x kg(-1), i.p.) partially attenuated LPS-induced myocardial depression. When these two drugs were simultaneously given, myocardial depression elicited by LPS was almost abolished. (3) LPS significantly decreased the amplitude of caffeine induced [Ca2+]i transients compared to the control cells. The activity of SR Ca22+ -ATPase was significantly decreased in the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG or BQ-123 did not attenuate the impairment of SR Ca2+ -ATPase induced by LPS.
CONCLUSIONET-1 and NO mediate myocardial dysfunction in hearts isolated and decrease [Ca2+]i transients in cardiac myocytes from LPS-treated rats. But neither ET-1 nor NO participates in the impairment of SR Ca2+ -ATPase induced by LPS.