title: Computational model of the ventricular action potential in adult spontaneously hypertensive rats.
abstract: BACKGROUND
  Cardiac hypertrophy has substantial clinical significance because many hypertrophic cells have markedly prolonged repolarization behavior, which may lead to increased risk for cardiac arrhythmias. Spontaneously hypertensive rat (SHR) is one model of hypertension that is studied extensively and is considered to be the best laboratory model of human hypertension. We extended our previously published model of the rat ventricular myocyte to simulate the effects of hypertrophy in SHR.
  
  
  RESULTS
  In SHR it has been shown that the membrane capacitance is increased, the density of transient outward K+ current is decreased, the sarcoplasmic reticulum Ca2+ ATPase activity is reduced, and the cell volumes are increased compared to those of the normal rat. We introduced these changes into our previous model of the rat ventricular myocyte and simulated the ventricular action potential of SHR. Our results demonstrated increased action potential duration (APD) and increased peak systolic value of the intracellular calcium transient in SHR. Simulations with reduced extracellular K+ concentration ([K+]o) have shown that there is increased APD shortening in SHR compared to that of the normal rat.
  
  
  CONCLUSIONS
  Our computational model qualitatively simulated the electrophysiologic changes observed in SHR and provided the plausible mechanistic linkage between the prolonged APD and increased inotropy. Our model results also demonstrated the electrophysiologic changes observed with reduced [K+]o in SHR, a finding that is clinically significant in hypertensive patients with left ventricular hypertrophy undergoing diuretic treatment.
authors.affiliation: Joint Graduate Program in Biomedical Engineering, The University of Memphis, Memphis, TN 38152-3210, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Padmala
authors.forename: Semahat S
authors.initials: SS
authors.lastname: Demir
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D006352:Heart Ventricles; D006973:Hypertension / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011930:Reaction Time; D013599:Systole; D016276:Ventricular Function
chemical_list: D007473:Ion Channels; D011188:Potassium; D002118:Calcium