Qd. Wang et al., LOCAL OVERFLOW AND ENHANCED TISSUE CONTENT OF ENDOTHELIN FOLLOWING MYOCARDIAL-ISCHEMIA AND REPERFUSION IN THE PIG - MODULATION BY L-ARGININE, Cardiovascular Research, 29(1), 1995, pp. 44-49
Objective: The local myocardial overflow and tissue content of endothe
lin-like immunoreactivity (ET-LIZ during ischaemia and reperfusion as
well as the coronary vascular effects of endothelin were characterised
in anaesthetised pigs. Methods: Ischaemia was induced by ligation of
the left anterior descending coronary artery for 45 min followed by 4
h of reperfusion. ET-LI was analysed in plasma from the anterior inter
ventricular coronary vein and aorta for estimation of local overflow a
nd in myocardial tissue. Endothelin analogues were given in the corona
ry artery for determination of local vascular effects. Results: During
reperfusion, but not during ischaemia, the veno-arterial concentratio
n difference of ET-LI increased, resulting in a significantly increase
d overflow at between 10 and 120 min of reperfusion. The tissue concen
tration of ET-LI in the left ventricle was seven times higher in the i
schaemic/reperfused area than in the non-ischaemic area: 161(SEM 30.5)
v 25.3(3.8) fmol.g(-1), P < 0.05. The increase in myocardial ET-LI wa
s attenuated by 70% (P < 0.01) by coronary venous retroinfusion of the
nitric oxide substrate L-arginine, whereas the overflow was unaffecte
d. Chromatographic characterisation of the myocardial ET-LI showed tha
t it was similar to endothelin-1. Intracoronary administration of endo
thelin-1, endothelin-3, and the endothelin ET(B) receptor agonist [Ala
(1,3,11,15)]]ET-1 evoked dose dependent coronary vasoconstriction, and
reductions in left ventricular dP/dt and arterial blood pressure. End
othelin-1 was two times more potent than endothelin-3 and 10 times mor
e potent than [Ala(1,3,11,15)]ET-1. Conclusions: Myocardial ischaemia/
reperfusion evokes enhanced local overflow of ET-LI during the reperfu
sion period combined with an increased tissue concentration of ET-LI w
hich is attenuated by L-arginine. Endothelin evokes potent coronary va
soconstriction via activation of both ET, and ET, receptors.