Relationship between coronary flow and high energy phosphates in the isolated perfused rat heart, with special reference to the effects of anoxia, iodoacetic acid, and 2,4-dinitrophenol.
In Langendorff rat hearts, anoxia increased the coronary flow, concentration of adenosine in the coronary effluent and the tissue level of lactate, and decreased the intracellular oxygen, left ventricular pressure (LVP), heart rate and the tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CrP). In the normoxic heart, an infusion of iodoacetic acid (IAA) (0.1 mg/min) increased the coronary flow, adenosine concentration in the effluent, and decreased ATP and CrP levels, without decreasing the intracellular oxygen. When glucose in the perfusate was substituted for pyruvate, IAA did not produce the pharmacological effects. In the normoxic heart, an infusion of 2,4-dinitrophenol (DNP) (50 micrograms/min) increased the coronary flow, adenosine concentration in the effluent and oxygen consumption, but decreased the intracellular oxygen, LVP and the tissue levels of ATP and CrP, without affecting the lactate level. There was no direct relationship between the coronary flow and the adenosine concentration in the effluent, but there was a close relationship between the increase in coronary flow and the total loss of myocardial ATP and CrP during anoxia, infusion of IAA, or infusion of DNP. These results indicate that the total loss of ATP and CrP from the myocardium (and hence energy state of the myocardium) may be responsible for regulation of coronary flow.
Shibano
T
T
Department of Pharmacology, Asahikawa Medical College, Japan.
Abiko
Y
Y
D019297:2,4-Dinitrophenol; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects*; D004140:Dinitrophenols / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012849:Sinoatrial Node / Q000187:drug effects / Q000378:metabolism
D004140:Dinitrophenols; D007461:Iodoacetates; D007773:Lactates; D009211:Myoglobin; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D019297:2,4-Dinitrophenol