MYOCARDIAL RELEASE OF ENDOTHELIN (ET) AND ENHANCED ET(A) RECEPTOR-MEDIATED CORONARY VASOCONSTRICTION AFTER CORONARY-THROMBOSIS AND THROMBOLYSIS IN PIGS
Qd. Wang et al., MYOCARDIAL RELEASE OF ENDOTHELIN (ET) AND ENHANCED ET(A) RECEPTOR-MEDIATED CORONARY VASOCONSTRICTION AFTER CORONARY-THROMBOSIS AND THROMBOLYSIS IN PIGS, Journal of cardiovascular pharmacology, 26(5), 1995, pp. 770-776
We investigated changes in vascular reactivity to endothelin (ET) and
local release of ET-like immunoreactivity (ET-LI) induced by myocardia
l ischemia and reperfusion in a pig model of coronary thrombosis and t
hrombolysis and studied the possible mechanisms producing the changed
vascular reactivity to ET-I, We induced coronary thrombosis by inserti
ng a copper coil into the left anterior descending coronary artery (LA
D) and achieved thrombolysis with tissue plasminogen activator (t-PA).
Vascular reactivity to ET-1 in the nonischemic and ischemic/reperfuse
d LAD diagonal branches was evaluated in vitro. ET-LI was analyzed in
plasma from the great cardiac vein and aorta for estimation of local r
elease. The vasoconstrictor response to ET-I was enhanced twofold (p <
0.01) in the ischemic/reperfused arteries as compared with the nonisc
hemic arteries, The vasoconstriction induced by the ET(B) receptor ago
nist [Ala(1,3,11,15)]ET-1 Or serotonin was not significantly affected
by ischemia/reperfusion. The ET(A) receptor antagonist BQ-123 reversed
the ET-l-induced vascular contraction to a similar degree in ischemic
/reperfused and control arteries. The ET-l-induced vasoconstriction of
control arteries was not affected by inhibition of nitric oxide (NO)
synthase with N-G-nitro-L-arginine (L-NNA) or cyclooxygenase with indo
methacin, During reperfusion, the myocardial venoarterial plasma conce
ntration difference of ET-LI and blood flow increased, resulting in an
increased overflow of ET-LI, Our results demonstrate that coronary th
rombosis and thrombolysis evokes enhanced local release of ET-LI durin
g the reperfusion period and increases the vasoconstrictor effects of
ET-1 through a mechanism related to ET(A) receptor activation but unre
lated to altered endothelial function. These changes may play a role i
n the development of ischemic/reperfusion injury and no-reflow phenome
non.