Nitric oxide (NO) has been implicated in the control of smooth muscle
tone, blood cell-vessel wall interactions, central and peripheral
neurotransmission and host defense mechanism. It is believed that NO has a
major role in mediating hypotension of endotoxemia and systemic inflammatory
response syndrome (SIRS).
The possibility of using NO synthesis inhibitors in the treatment of these
disorders was emerging as a novel therapy but it was associated with deleterious
side effects. An ideal approach would be the binding of excess-free NO in the
vasculature. The cobalt atom of hydroxocobalamin (Of-IC) efficaciously binds
cyanide and NO.
The present study aimed to test the effect of OHC on the hypotension
induced by NO producing agents such as acetylcholine (Ach) and Na
nitroprusside versus its effect on the hypotension induced by the non-specific
vasodilator papaverine in rats. The interactions of OlIC with Ach, Na
nitroprusside & papaverine on the isolated rabbit aortic strip were also studied.
It was found that OHC (20mg/kg i.v) produced a significant (p<0.05)
attenuation of the Ach and Na nitroprusside-induced hypotension in rats as well
as a significant (p<0.05) dose-dependent attenuation of the relaxation induced by
these agents on the isolated rabbit` aortic strip. On the other hand it was fond
that OHC had insignificant (p>0.05) changes on the papaverine-induced
hypotension in rats as well as insignificant (p0.05) changes on the relaxation
induced by papaverine on the isolated rabbit aortic strip.
In conclusion, 011C could attenuate the vascular responses to NO, an
action which may be of beneficial clinical uses in preventing and improving the
hemodynatnic sequelae of septic shock, SIRS and other disorders associated with
NO overproduction. |
