Adrenergic stimulation of rat hearts with severely reduced cytosolic adenine nucleotide pool and [ATP]/[ADP]ratio.
The effect of severe reduction of cytosolic adenine nucleotide (AdN) pool and [ATP]/[ADP] ratio (by 2-deoxyglucose treatment) on functional and metabolic responses of isovolumic rat heart to increased energy demand induced by coronary flow (CF) rise and isoproterenol (Iso) addition has been investigated. AdN-depleted hearts had reduced phosphocreatine (PCr, by 80%), ATP (by 75%), [ATP]/[ADP] (24 times) and pressure-rate product (PRP, by 60%). An elevation of CF was followed by the increase in PRP in control and AdN-depleted hearts by 40-45% with unchanged metabolic parameters. At increased CF, Iso caused a further rise in PRP in both groups due to elevation of heart rate; however maximal levels of PRP in the AdN-depleted group still remained lower than that of control (by 40%). Only in control experiments was Iso addition accompanied by an increase in the difference between left-ventricular end- and minimal diastolic pressure, cytosolic [Pi] and [ADP], and some decrease in PCr and [ATP]/[ADP]. These data imply that severely reduced cytosolic [ATP]/[ADP] does not prevent acceleration of Ca2+ turnover by Iso in cardiomyocytes, it but restricts maximal force development affecting the myofibrils.
Kupriyanov
V V
VV
Institute of Experimental Cardiology, Russian Cardiology Research Center, Academy of Medical Sciences, Moscow.
Korchazhkina
O V
OV
Lakomkin
V L
VL
Kapelko
V I
VI
D000227:Adenine Nucleotides / Q000172:deficiency*; D000244:Adenosine Diphosphate / Q000172:deficiency; D000255:Adenosine Triphosphate / Q000172:deficiency; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007545:Isoproterenol