Steady-state catecholamine stimulation does not increase cytosolic adenosine in canine hearts.
Myocardial adenosine production increases transiently during the onset of catecholamine stimulation; however, there is conflicting evidence regarding whether cytosolic adenosine concentrations are increased during sustained steady-state stimulation. If cytosolic adenosine is not elevated during steady-state stimulation, then adenosine produced in the cytosol does not play a role in mediating the sustained increase in myocardial blood flow. The purpose of the present study was to determine whether cytosolic adenosine concentrations in the anesthetized dog heart are increased during steady-state stimulation with norepinephrine, epinephrine, and atrial pacing. Regional cytosolic adenosine concentrations were assessed by measuring myocardial content of S-adenosyl-L-homocysteine (SAH) after 20 min of intravenous administration of L-homocysteine thiolactone. Excess homocysteine causes myocardial accumulation of SAH at a rate dependent on the cytosolic concentration of adenosine. Steady-state metabolic stimulation caused more than twofold increases in myocardial blood flow and oxygen consumption, but there was no increase in left ventricular content of SAH in the stimulation group [6.3 +/- 0.9 nmol/g (SE); n = 6] relative to a parallel unstimulated control group (6.4 +/- 0.9 nmol/g; n = 6). The transmural distribution of SAH was nearly uniform, and there was no correlation between regional measurements of blood flow and myocardial content of SAH or ATP either during metabolic stimulation or under control conditions. In separate experiments, myocardial ischemia caused fivefold increases in SAH content, confirming the sensitivity of the SAH method for increased cytosolic adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
Kroll
K
K
Center for Bioengineering, University of Washington, Seattle 98195.
Martin
G V
GV
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002304:Cardiac Pacing, Artificial; D002395:Catecholamines / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006711:Homocystine / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D012016:Reference Values; D012435:S-Adenosylhomocysteine / Q000378:metabolism
D002395:Catecholamines; D006710:Homocysteine; D006711:Homocystine; D000255:Adenosine Triphosphate; D012435:S-Adenosylhomocysteine; C007957:homocysteine thiolactone; D000241:Adenosine