LOCAL OVERFLOW AND ENHANCED TISSUE CONTENT OF ENDOTHELIN FOLLOWING MYOCARDIAL-ISCHEMIA AND REPERFUSION IN THE PIG - MODULATION BY L-ARGININE

Citation
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
Citations number
31
Categorie Soggetti
Cardiac & Cardiovascular System
Journal title
ISSN journal
00086363
Volume
29
Issue
1
Year of publication
1995
Pages
44 - 49
Database
ISI
SICI code
0008-6363(1995)29:1<44:LOAETC>2.0.ZU;2-J
Abstract
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.