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The purposes of these studies were to investigate the
antihypertensive and antiplatelet aggregation effects of
DC-015, and compare with prazosin. In anaesthetized
spontaneously hypertensive rats (SHR), intravenous
administration of DC-015 and prazosin (0.01, 0.05, 0.1 mg/kg)
induced a dose-related reduction of mean blood pressure (MBP)
which reach a maximal effect at 5 min after injection and
persisted for more than 2 hours. Oral administration of DC-015
(1.0, 2.0 mg/kg) in anaesthetized SHR also caused a dose-
related reduction of MBP which reached a maximal effect 10 min
after oral administration and persisted for over 3 hours. The
potency of antihypertensive effect showed no significant
difference between DC-015 and prazosin by oral administration.
Otherwise, both DC-015 and prazosin significantly attenuated
pressor responses to phenylephrine but failed to angiotensin II
even at maximal hypotensive dose. In vitro study demonstrated
that DC-015 was found to be a potent alpha1-adrenoceptor
blocking agent which shows a competitive antagonism of
phenylephrine (pA2 =10.20 .plmin. 0.04) in rat thoracic aorta.
The pA2 value of DC-015 was showed less potent than prazosin
(pA2 = 11.16 .plmin. 0.03). However, the antagonism effect of
DC-015 (10 .mu.M) to 5-HT is more potent than prazosin (10 .mu.
M), the IC50 was 88.2 .mu.M vs. 11.1 .mu.M . On the other hand,
DC-015 (2 .mu.M) can significantly inhibit NE (10 .mu.M)
induced aggregation in human platelet-rich plasma and IC50 =
5.94 .mu.M. Meanwhile, IC50 of prazosin was 66.2 .mu.M .
However, DC-015 and prazosin did not effect the tail bleeding-
time in mice. In receptor binding assays, the alpha2/alpha1
ratio of DC-015 was 2824 and prazosin was 25421. In conclusion,
DC-015 is a potent and selective alpha1- adrenoceptor
antagonist, which can significantly reduces blood pressure in
anaesthetized SHR. In addition, DC-015 can also inhibit
platelet aggregation by alpha2-blocking activity.
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