Wz. Wang et al., ENDOTHELIN-1 DOES NOT CONTRIBUTE TO ISCHEMIA REPERFUSION-INDUCED VASOCONSTRICTION IN SKELETAL-MUSCLE/, Journal of reconstructive microsurgery, 13(6), 1997, pp. 439-447
The experiment reported was designed to investigate whether endothelin
-1 (ET-1) contributes to vasospasm and poor perfusion during the reper
fusion after prolonged ischemia in skeletal muscle. Male Sprague-Dawle
y rats weighting 100 to 120 g were anesthetized with Nembutal. The vas
cular isolated rat cremaster muscle, coupled with local interarterial
infusion, was the model used in this study. The diameters of feeding a
rterioles and terminal arterioles were measured utilizing intravital m
icroscopy. The number of terminal arterioles with temporary cessation
of flow were counted in each cremaster. Group 1: ET-dose response (8 r
ats)-various concentrations of ET-1 (from 10(-8) M to 10(-5) M) were i
nfused into the cremaster to test whether this muscle was responsive t
o the agent in a dose-dependent manner. Group 2: ET-antagonist respons
e (12 rats)-PD-142893, 10(-4) M (ETab receptor antagonist) plus ET-1 1
0(-7) M were infused into the cremaster to test whether vasospasm caus
ed by exogenous ET-1 could be prevented by pretreatment with this spec
ific ETab receptor antagonist. Group 3: ischemia/reperfusion response
(12 rats)-PD-142893, 10(-4) M was infused into the cremaster before is
chemia (4 hr warm ischemia) and during reperfusion to test whether ETa
b receptor antagonism was effective in preventing the vasospasm associ
ated with ischemia/reperfusion injury. The results from this study sho
w that a mixed ETab endothelin antagonist, PD-142893, infused before i
schemia and during reperfusion at a dose which virtually abolished the
vasoconstriction produced by a high concentration of exogenous endoth
elin-1, had no effect on ischemia/reperfusion-induced vasoconstriction
in this model. These results suggest that ET-1 probably does not cont
ribute to the ischemia/reperfusion-induced vasoconstriction and poor r
eflow in rat skeletal muscle.