The role of nitric oxide in mediating endothelium dependent relaxations in the human epicardial coronary artery.
We have examined the ability of the endothelium of human epicardial coronary arteries to secrete vasorelaxant substances in response to pharmacological stimulation and under basal conditions. In addition, we have attempted to characterise the chemical identity and biochemical pathway for the synthesis of endothelial derived relaxing factor. Human epicardial coronary arteries were removed from patients who were undergoing heart transplantation for reasons other than ischaemic heart disease. Arteries were cut into segments and suspended in 5 ml organ baths containing a modified Tyrodes solution at 37 degrees C, and gassed with a mixture of 95% oxygen and 5% carbon dioxide. Substance P (10(-10) - 10(-7) M) elicited a dose-dependent relaxation of the coronary segments but this action of substance P was dependent upon an intact endothelium. The maximum response of substance P was equivalent to 89 +/- 8.5% of the maximum effect induced by 1 microgram/ml glyceryl trinitrate. This vasorelaxant effect of substance P was unaffected by the presence of 10(-6) M indomethacin. L-NG-monomethyl-arginine (10(-4) M), a specific inhibitor of formation of nitric oxide from L-arginine, antagonised the relaxations induced by substance P, decreasing the maximum response of substance P to 34 +/- 10.5% of the response to glyceryl trinitrate. Upon application, L-NG-monomethyl-arginine caused a further 23.1 +/- 3.0 increase in tension on preconstricted vessels. This increase in tension was reversed with the addition of L-arginine, but was unaffected by D-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
Chester
A H
AH
National Heart & Lung Institute, Department of Cardiothoracic Surgery, Harefield, Middlesex, U.K.
O'Neil
G S
GS
Tadjkarimi
S
S
Palmer
R M
RM
Moncada
S
S
Yacoub
M H
MH
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007223:Infant; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013373:Substance P / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D007213:Indomethacin