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EC number: 248-363-6
CAS number: 27247-96-7
The cardiovascular effects of equimolar doses of organonitrates
including the registered substance 2-Ethylhexyl nitrate (CAS 27247-96-7)
as mononitrate, Propylene glycol dinitrate (CAS 6423-43-4) and
Nitroglycerin (CAS 55-63-0, positive control) as trinitrate were
comparatively investigated employing an antihypertensive assay.
Using a volume of 2 mL/kg bw, ten groups of 6 male Spontaneously
Hypertensive (SH) rats received one intra-arterially treatment with 0.8,
4 or 8 µmol/kg bw of each test item (50 % ethanol solution) or the
vehicle control. Intentionally the vehicle control increased all
parameters monitored, which were Systolic blood pressure, Diastolic
blood pressure and the Heart rate.
All tested organonitrates antagonize the increase of systolic and
diastolic blood pressure caused by the vehicle and have little effect on
the heart rate seemingly causing a slightly higher increase as the
vehicle alone (weak synergism).
The comparison of tri-, di-, and mononitrate substances reveals by
tendency that the organonitrates act similarly on heart rate and blood
pressure, but the trinitrate clearly has a stronger effect, demonstrated
by the fact that only with this agent statistical significance was
reached in all tested levels. No difference in the strength of effects
is visible between the di- and the mononitrate, but the statistical
power is low and only a few treatments were statistically different to
the pre-exposure measurements.
In conclusion organonitrates act similarly on heart rate and blood
pressure in the experimental setting used. While the trinitrate had a
stronger effect, demonstrated by the fact that only the positive control
statistical significance was reached in all tested levels, no difference
in the strength of effects is visible between the di- and the
mononitrate. Considering the equimolar doses, the potential Nitrogen
monoxide release (known to be the pharmacological principle of
Nitroglycerin) was three times higher than the one of 2-Ethylhexyl
nitrate.This suggests that GDN will serve as a worst case scenario for
2-EHN, and PGDN will provide satisfactory read across data for 2-EHN.
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