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Endothelium-derived relaxing factor in human coronary artery in vitro
1992
43
Annual
Scientific
Meeting:
Australasian
and
New
Zealand
Section
ENDDTHELIDM-DERIVED RELAXING FACTOR IN HIJHAN CORONARY ARTERY IN VITRO. Andrew P. Stork & Tom M. Cocks. Baker Medical Research Institute, Victoria, Australia. Coronary artery rings from explanted human hearts were precontracted with the thromboxane A2-mimetic U46619 (3nM) in the presence of nifedipine (O.luMM). Substance P, bradykinin and histamine all caused concentrationand endotheliumdependent relaxation. In the absence of endothelium, histamine caused concentration-dependent contraction. Acetylcholine and serotonin only ever caused contraction of this tissue. Substance P was the most potent and efficacious of the EDRT agonists studied maximum (EC50=115t30pM, response=14.95*3.71% of constrictor tone, n=ll). The vasorelaxant profiles of histamine and bradykinin were not altered by indomethacin (3-10!.1M), indicating that prostacyclin production did not significantly contribute to the response. The L-arginine analogues NG-nitro-L-arginine (NOLA;lOO@l) and NGmonomethyl-L-arginine (LNMMA;lOOuM) inhibited endothelium-dependent relaxations (eg. Substance P with NOLA: EC50=234*45pM, max.=30.46*7.25%, n=lO; with LNMMA: EC50=204*49pM, max.=41.26*7.20%, n=7). Increasing levels of active tone also significantly reduced both the potency and maximum response to substance P, isoprenaline and SNP. Thus both agonist efficacy and functional antagonism need to be considered when evaluating vasorelaxants in human isolated coronary artery.
xvii
43
Annual
Scientific
Meeting:
Australasian
and
New
Zealand
Section
ENDDTHELIDM-DERIVED RELAXING FACTOR IN HIJHAN CORONARY ARTERY IN VITRO. Andrew P. Stork & Tom M. Cocks. Baker Medical Research Institute, Victoria, Australia. Coronary artery rings from explanted human hearts were precontracted with the thromboxane A2-mimetic U46619 (3nM) in the presence of nifedipine (O.luMM). Substance P, bradykinin and histamine all caused concentrationand endotheliumdependent relaxation. In the absence of endothelium, histamine caused concentration-dependent contraction. Acetylcholine and serotonin only ever caused contraction of this tissue. Substance P was the most potent and efficacious of the EDRT agonists studied maximum (EC50=115t30pM, response=14.95*3.71% of constrictor tone, n=ll). The vasorelaxant profiles of histamine and bradykinin were not altered by indomethacin (3-10!.1M), indicating that prostacyclin production did not significantly contribute to the response. The L-arginine analogues NG-nitro-L-arginine (NOLA;lOO@l) and NGmonomethyl-L-arginine (LNMMA;lOOuM) inhibited endothelium-dependent relaxations (eg. Substance P with NOLA: EC50=234*45pM, max.=30.46*7.25%, n=lO; with LNMMA: EC50=204*49pM, max.=41.26*7.20%, n=7). Increasing levels of active tone also significantly reduced both the potency and maximum response to substance P, isoprenaline and SNP. Thus both agonist efficacy and functional antagonism need to be considered when evaluating vasorelaxants in human isolated coronary artery.
xvii