Perfused rat hearts were used to study the effects of
acidosis on coronary tone. When pH was decreased, over the range pH 7.4 to pH 6.2, by reducing perfusate
bicarbonate levels, under constant flow conditions, there was a transient decrease in coronary perfusion pressure (
CPP), followed by a sustained
acidosis-dependent increase in
CPP, which reversed when pH was returned to pH 7.4. This increase in
CPP was seen at perfusion rates of 5, 10, and 20 ml/min(-1). When using constant pressure perfusion
acidosis reduced coronary flow. In a
HEPES-buffered
bicarbonate-free
solution,
acidosis did not cause a transient fall in
CPP but it did produce a sustained increase in
CPP. Addition of
ammonium chloride (10 mM) reduced
CPP, while washout of
ammonium chloride increased
CPP. The
acidosis-induced increase in
CPP was not affected by
indomethacin, nitro-
L-arginine, the nonselective
adenosine receptor antagonist, 8-phenyl
theophylline, or the
thromboxane receptor antagonist,
ZD 1542. The
acidosis-induced increase in
CPP was independent of the
myocardial depressant effects of
acidosis, but was attenuated by three different
L-type calcium channel blockers. These results demonstrate that the coronary circulation of the rat constricts in response to
acidosis. Experiments performed with
L-type calcium channel blockers, and the
calcium channel activator
BAY K8644, suggest that constriction occurs via activation of
L-type calcium channels. This would not be expected on the basis of electrophysiological studies, which have shown an inhibition of
L-type calcium channels by
acidosis.