Implication of Substance P in myocardial contractile function during ischemia in rats.
Evidence suggests that substance P (SP) participates in the pathology of acute myocardial ischemia and infarction but the profiles of the peptide in regulation of cardiac functions are still elusive. The aim of this study was to investigate the role of substance P in regulation of cardiac functions and its association with adrenergic mechanism in acute myocardial ischemia and infarction with rodent models. The experiments were carried out in Sprague-Dawley rats. SP and norepinephrine were significantly up-regulated in myocardium at 15min, 30min and 60min of coronary artery occlusion. Pretreatment of the rats with a specific antagonist of neurokinin-1 receptor, D-SP, significant increased+dp/dt and decreased -dp/dt, compared with the controls, pretreated with 0.9% saline. Pretreatment of the isolated CAO hearts with substance P (10(-7)mol/L) significantly increased left ventricular end diastolic pressure. SP producing no effects on cardiac functions when given alone to isolated (non-CAO) heart caused significant attenuation of the changes in the contractility and diastolic functions induced by norepinephrine, when given with norepinephrine. SP attenuated the increase in the activity of PKA provoked by norepinephrine in cultured myocytes. In conclusion, the findings may indicate SP regulates cardiac functions via modulation of adrenergic activity, through suppression of over-activation of PKA.
Departments of Anesthesiology, Shanxi Medical University and Second Hospital of Shanxi Medical University, 56 South Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China.
Li-Li
LL
Wang
Zheng
Z
Guo
Yi
Y
Han
Peng-Fei
PF
Wang
Ri-Lin
RL
Zhang
Yan-Li
YL
Zhao
Fu-Ping
FP
Zhao
Xiao-Ying
XY
Zhao
D000818:Animals; D003971:Diastole / Q000187:drug effects; D004195:Disease Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P