Endocardial endothelium is a key determinant of force-frequency relationship in rat ventricular myocardium. 2013

Xiaoxu Shen, and Zhen Tan, and Xin Zhong, and Ye Tian, and Xian Wang, and Bo Yu, and Genaro Ramirez-Correa, and Anne Murphy, and Kathleen Gabrielson, and Nazareno Paolocci, and Wei Dong Gao
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

We tested the hypothesis that removing endocardial endothelium (EE) negatively impacts the force-frequency relationship (FFR) of ventricular myocardium and dissected the signaling that underlies this phenomenon. EE of rat trabeculae was selectively damaged by brief (<1 s) exposure to 0.1% Triton X-100. Force, intracellular Ca(2+) transient (iCa(2+)), and activity of protein kinase A (PKA) and protein kinase C (PKC) were determined. In control muscles, force and iCa(2+) increased as the stimulation frequency increased in steps of 0.5 Hz up to 3.0 Hz. However, EE-denuded (EED) muscles exhibited a markedly blunted FFR. Neither isoproterenol (ISO; 0.1-5 nmol/l) nor endothelin-1 (ET-1; 10-100 nmol/l) alone restored the slope of FFR in EED muscles. Intriguingly, however, a positive FFR was restored in EED preparations by combining low concentrations of ISO (0.1 nmol/l) and ET-1 (20 nmol/l). In intact muscles, PKA and PKC activity increased proportionally with the increase in frequency. This effect was completely lost in EED muscles. Again, combining ISO and ET-1 fully restored the frequency-dependent rise in PKA and PKC activity in EED muscles. In conclusion, selective damage of EE leads to significantly blunted FFR. A combination of low concentrations of ISO and ET-1 successfully restores FFR in EED muscles. The interdependence of ISO and ET-1 in this process indicates cross-talk between the β1-PKA and ET-1-PKC pathways for a normal (positive) FFR. The results also imply that dysfunction of EE and/or EE-myocyte coupling may contribute to flat (or even negative) FFR in heart failure.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002316 Cardiotonic Agents Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right

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