الفهرس 
Material and methodsOnly 14 pages are availabe for public view
 |  | from | 260 |  |  |
| | | from | 260 | | |
Abstract
In the present study. it was found that intravenous
administration of Captopril in doses ranging from 1 to 160
~g/kg. in normotensive anaesthetized cats. induced a gradual
and sustained fall in the mean arterial blood pressure.
meanwhile. in normotensive anaesthetized rats. it produced a
transient fall in the mean blood pressure followed by slow.
return to normal levels. However. in unilateral
nephrectomized plus DOCA/salt hypertensive rats. captopril
induced a gradual and sustained decrease in the mean blood
pressure which was dose-related and persisting far more than
one hour. Meanwhile in DOCA/salt hypertensive anaesthetized
rats. it induced a slow but sustained fall in arterial blood
pressure.
The antihypertensive effect of captopril may be
related to the inhibition of the formation of A II locally in
the vascular tissues or due to its reducing effect on the
sympathetic sensitivity and total peripheral resistance.
Moreover. captopril was demonstrated to potentiate the
hypotensive effect of bradYkinin in DOCA/salt hypertensive
rats. This effect might be through its inhibitory action on
kinin degradation with potentiation of the vasodilator effect
of bradYkinin.
-213-
In vitro. the data of our work showed that captopril
in doses ranging from 1 to 32 ~g/ml attenuated the
norepinephrine induced contractions of the isolated rabbit’s
thoracic aorta~. Thus, captopril could reduce the sensitivity
of the vasculature to vasoactive agents and it _ight be
contributed partly to its antihypertensive mechanisms.
In the
0.1 to 4
present work, captopril in doses ranging from
~g/ml attenuated the norepinephrine induced
contractions of non-vascular smooth muscle (guinea pig vas
deferens).
Captopril. in the present study, did not produce any
significant effect on the amplitude of normal myocardial
contractility of isolated rabbit’s hearts, while, it induced
insignificant inhibitory effect on the atrial rate of the
isolated rabbit’s hearts.
Moreover, it was found that, captopril administration
intravenously in doses of 100 ~g/kg induced a significant
reduction in the vasopressor responses of A I, recovery
occurs within one hour. in normotensive and in two models of
hypertensive anaesthetized rats.
As regards A
intravenous captopril
11. it was found that, small doses of
ranging from 1 to 20 ~g/kg attenuated
-214-
while larger doses ranging from 80 to 160 ~g/kg enhanced the
vasopressor responses elicited by A II in chloralosed
normotensive anaesthetized cats.
Meanwhile. in rats. intravenous administration of
captopril in a dose of 100 ~g/kg induced enhancement of the
vasopressor responses to A II (100 ng/kg) in normotensive and
two models of hypertensive anaesthetized rats. This
increase in sensitivity to exogenous A II in captopril
pretreated animals was thought to be related to the decrease
in circulating endogenous A II which may result in greater
availability (sensitivity) of vascular receptors sites to
exogenous A II.
Furthermore. in vitro studies on the isolated rabbit’s
aortic strips. captopril showed that in relatively small
concentrations attenuated. the contractile responses elicited
by A II more than by norepinephrine. revealing the relative
potency and specificity inhibition of angiotensin converting
enzyme.
Moreover. captopril potentiated the vasodepressor
effects induced by bradykinin in both normotensive and
hypertensive anaesthetized rats. Captopril. however.
augmented the bradykinin-induced contractions of the isolated
guinea pig ileum.
-215-
Thus, the potentiating effect of captopril on
bradykinin effects may be attributed to its inhibitory effect
on kinnase II, which lead to preservation of bradYkinin from
degradation.
In the present study, captopril increased the basal
tone of isolated rabbit’s jejunum and guinea pig tracheal
strips in a dose-related manner.
However, captopril in a dose of 100 /,g!kgproduced
negligible increase in the vasopressor responses to «-
adrenoceptor stimulants including norepinephrine, phenylepherine
and guanfacine in normotensive and DOCA!salt
hypertensive anaesthetized rats. Thus, single smaller dose
of captopril not enough to produce a selective inhibitory
effect on the vascular responses to sympathomimetics.
In the present study, myocardial necrosis was experimentally induced by subcutaneous injection of
isoprenaline in a dose of 300 mg!kg. The electrocardiograph
tracing showed sinus tachycardia with injury currents in form
of inverted or highly peaked T-wave.
In this study, serum creatinine phosphokinase CPK
level increased to 868 ±15 U!l in rats 6 hours after
subcutaneous injection of isoprenaline. The average size of
necrotic foci was 33 ±3% and they were found to be scatterad
-216-
on both ventricles and interventricular septum.
The degree of protective effect induced by captopril
was evaluated by studying the changes in the severity of the
cardionecrosis evoked by isoprenaline in rats.
Injection of captopril in a dose of 100 ~g/kg 15
minutes before the subcutaneous injection of isoprenaline
minimized the size of necrotic foci to 10 ±i% and the level
of CPK to 316 ±13 U/l. Moreover, ECG indicates the
pretreatment with captopril in a dose of 100 ~g/kg, as it
prevented completely the occurrence of the injury currents.
However, post-treatment with captopril produced a
protective effect on the rats myocardium against isoprenaline
induced myocardial necrosis but in a time dependent manner.
In conclusion, captopril induced an obvious and marked
DROP in blood pressure in experimentally induced hypertensive
rats. Moreover, captopril attenuated the vasopressor
response of angiotensin I, whereas potentiated the
vasopressor angiotensin II and vasodepressor response of
bradykinin in both normotensive and hypertensive rats.
Moreover, captopril did not modify significantly the
inotropic and chronotropic properties of the isolated
rabbit’s heart. Furthermore, captopril reduced the isolated
rabbit’s aortic strip response to angiotensin II, and
norepinephrine. Meanwhile,
effect on experimentaly
isoprenaline in rats.
-217-
captopril has cardioprotective
induced myocardial necrosis with isoprenaline in rats.