AJP - Heart and Circulatory Physiology, Vol 266, Issue 2 503-H510, Copyright © 1994 by American Physiological Society
Steady-state catecholamine stimulation does not increase cytosolic adenosine in canine hearts
K. Kroll and G. V. Martin
Center for Bioengineering, University of Washington, Seattle 98195.
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)
