objective:To examine the dose-dependent effects of endothelin-1 (ET-1) on both cardiac function and myocardial metabolism. Methods: lsolated working rat hearts were perfused by oxygenated Krebs buffer with 13 C-enric...objective:To examine the dose-dependent effects of endothelin-1 (ET-1) on both cardiac function and myocardial metabolism. Methods: lsolated working rat hearts were perfused by oxygenated Krebs buffer with 13 C-enriched substrates (1. 0 mmol/L [3-13C] lactate and 0. 25 mmol/L [1,2~13C ] acetate) ; ET-1 was added to the perfusate to produce an estimated circulating concentration of 6O pmol/L (ET60) or 600 pmol/L (ET600). Myocardial energy metabolism and substrate utilization were analyzed by multi-nuclear (31P and 13 C) magnetic resonance (NMR) spectroscopy. Meantime, cardiac output (CO), coronary flow (CF) and left ventricular developed pressure (LVDP) were recorded (Millar catheter). Results: CT decreased when ET-1 level enhanced (- 30% for ET60 group and - 42% for ET600 group,Pr0. 05). CO transiently increased above control but fell after 35 min infusion (-4% in ET60 group and - 23% in ET600 group respectively,P <0. 05). LVDP was also decreased at the end of ET per fusions. 31P NMR spectroscopy showed a decrease in cellular phosphorylation potential ([ATP]/[ADP][Pi]) when ET-1 level increased (y= 5. 2303e-2-5. 517le 5x R ~ 2= 0. 885). However, It is interesting that the PCr/ATP ratio decreased only in ET6O group, while in ET6oo group the further decrease of [ATP]/[ADP][Pi] did not company a further decrease in PCr/ATP. This phenomenon may suggest an inhibition of CPK activity under the circumstance of high ET-1 level. 13C NMR spectroscopy showed an ET-1 mediated inhibition on exogenous lactate utilization. Conclusion: (1)En dothelin-1 has either a directly positive inotropic effect on isolated perfused rat hearts or an indirectly negative inotropic effect through reduced coronary flow; (2)High level ET-1 may decrease myocardial phosphorylation potential and inhibit CPK activity as well ; (3)Acetate is a better substrate comparing to lactate for myocardium of the patients with increased systemic ET levels.展开更多
文摘objective:To examine the dose-dependent effects of endothelin-1 (ET-1) on both cardiac function and myocardial metabolism. Methods: lsolated working rat hearts were perfused by oxygenated Krebs buffer with 13 C-enriched substrates (1. 0 mmol/L [3-13C] lactate and 0. 25 mmol/L [1,2~13C ] acetate) ; ET-1 was added to the perfusate to produce an estimated circulating concentration of 6O pmol/L (ET60) or 600 pmol/L (ET600). Myocardial energy metabolism and substrate utilization were analyzed by multi-nuclear (31P and 13 C) magnetic resonance (NMR) spectroscopy. Meantime, cardiac output (CO), coronary flow (CF) and left ventricular developed pressure (LVDP) were recorded (Millar catheter). Results: CT decreased when ET-1 level enhanced (- 30% for ET60 group and - 42% for ET600 group,Pr0. 05). CO transiently increased above control but fell after 35 min infusion (-4% in ET60 group and - 23% in ET600 group respectively,P <0. 05). LVDP was also decreased at the end of ET per fusions. 31P NMR spectroscopy showed a decrease in cellular phosphorylation potential ([ATP]/[ADP][Pi]) when ET-1 level increased (y= 5. 2303e-2-5. 517le 5x R ~ 2= 0. 885). However, It is interesting that the PCr/ATP ratio decreased only in ET6O group, while in ET6oo group the further decrease of [ATP]/[ADP][Pi] did not company a further decrease in PCr/ATP. This phenomenon may suggest an inhibition of CPK activity under the circumstance of high ET-1 level. 13C NMR spectroscopy showed an ET-1 mediated inhibition on exogenous lactate utilization. Conclusion: (1)En dothelin-1 has either a directly positive inotropic effect on isolated perfused rat hearts or an indirectly negative inotropic effect through reduced coronary flow; (2)High level ET-1 may decrease myocardial phosphorylation potential and inhibit CPK activity as well ; (3)Acetate is a better substrate comparing to lactate for myocardium of the patients with increased systemic ET levels.
