Adenosine is known to participate in the regulation of
several circulatory functions. Its action is mediated through
distinct receptor subtypes mainly located in myocardial and
vascular endothelial and smooth muscle cells. The hypotensive
and vasodilator effect of exogenously administered adenosine
has been previously described. However, a vasoconstrictor action
of adenosine on some vascular beds has also been reported.
This study was designed to explore the effect of modifying trie
concentration of endogenous adenosine on the blood flow through
three different arterial resistance beds (renal, mesenteric and
hindquarters vascular beds). Augmentation of endogenous
adenosine concentration was achieved via the use of two agents
with two different modes of action: monophosoryl lipid A (MLA),
the 5 nucleotidase activator and nitrobenzylthioinosine (NBMPR),
the adenosine transport blocker. These two mechanisms lead
to the accumulation of both extracellular and intracellular
adenosine. MLA and NBMPR were infused in two different
dose levels and blood flow through the renal, mesenteric and
inferior abdominal aorta was detected using flow probe connected
to electromagnetic flowmeter. MLA in low dose induced
renal and mesenteric vasodilatation but no change in hindquarters
blood flow. In contrast, high dose of MLA induced
hypotension, bradycardia, renal and hindquarters vasoconstriction
and no change in nit:enteric uluod flow. NBMPR produced
qualitatively similar but quantitatively different results. The
adenosine (Al and A2) receptor antagonist, 8 p-sulfophenyl
theophylline (8SPT) abolished the vasodilator but not the vasoconstrictor
effects of both drugs indicating that the vasoconstrictor
effects are either indirect through hypotension induced pressor refelexs, or mediated through different adenosine
receptor subtype. The dual effect of adenosine may suggest
an important role in regulation of these organs blood flow |
