|
THE INFLUENCE OF DIFFERENT CALCIUM
CHANNEL ANTAGONISTS ON CORONARY CIRCULATION OF THE ISOLATED RAT
HEART: INTERACTION WITH L-ARGININE: NO SYSTEM
,
,
,
,
,
,
|
|
ABSTRACT
The aim of the study was to assess
the interactions between different classes of Ca
channel antagonists and endothelial L-Arginine/NO system, like a
dominant metabolic control system.
Hearts from male Wistar albino rats (age 8 weeks, BM=180-200 g)
were used and perfused according to Langendorff technique at constant
pressure conditions. After stabilization of the preparation (30
min at 60 cm HO),
perfusion pressure (CPP) has been gradually increased from 40 to
120 cm HO
and coronary flow (CF), release of NO (as nitrite concentration)
were measured. Experiment were performed during control condition
and in the presence of different Ca
channel antagonists: nifedipine (30 nM), diltiazem (3 µM),
verapamil (0.4 µM),
amlodipine (0.05 mg/l) alone and dyhydropiridines in combination
with NO synthase inhibitor L-NAME (30 µM).
Isolated rat hearts exhibit autoregulation of coronary flow (CF)
between 50 and 90 cm H2O of coronary perfusion pressure (CPP). Basal
release measurement (at 60 cm HO)
of NO was 1.80±0.22 nmol/min/ g/wt and was strictly parallel
with CPP-CF curve.
Autoregulatory range of CF was significantly extended (40-100 cm
HO)
under influence of nifedipine, while otber Ca
channel antagonists didn’t changed coronary autoregulation.
Changes in NO-release were parallel with CPP- CF curve, except in
amlodipine-experiments, when nitrite-release was significantly reduced.
When L-NAME and dyhydro- piridines were applied together, CF was
significantly reduced, with parallel changes of NO-release.
Our results showed that action of Ca
channel antagonists is in interaction with L-Arginine/NO system
in coronary circulation of the isolated rat heart, with highest
efficiacy of amlodipine.
Keywords: nitric oxide - Ca
channel antagonists - coronary autoregulation - rat heart
|
