NUCLEOTIDE-EVOKED RELAXATION OF HUMAN CORONARY-ARTERY

Endothelium-dependent dilation of coronary blood vessels in response t o ATP and related nucleotides has been demonstrated in various animal species. The aim of the present study was to investigate a possible re laxant effect of ATP, the adenine nucleotides 2-methylthio ATP (MeSATP ) and adenosine 5'-O-(2-thiodiphosphate) (ADP beta S), and the pyrimid ine nucleotide UTP in isolated human coronary artery. In endothelium-i ntact rings of human coronary artery precontracted with K+ (20-40 mM), the nucleotides caused relaxation. Average maximal percentage relaxat ions and average EC50 values (concentrations causing half-maximal rela xation) were 89% and 47.1 mu M for ATP, 28% and 0.3 mu M for MeSATP, 3 5% and 0.6 mu M for ADP beta S, and 49% and 1.6 mu M for UTP. For each of the four agonists, the potency to elicit relaxation varied greatly between individual rings, so that equi-relaxing concentrations spanne d several orders of magnitude. Moreover, the sensitivities to ATP and UTP, when tested in the same ring, were not correlated. Mechanical rem oval of the endothelium as well as N-G-nitro-L-arginine methyl ester ( L-NAME; 30 mu M), an inhibitor of nitric oxide synthase, abolished the relaxation caused by MeSATP, ADP beta S and UTP and greatly attenuate d the response to lower concentrations of ATP (3.2-320 mu M), but high concentrations of ATP (320 and 1000 mu M) caused relaxation also in e ndothelium-denuded preparations and in the presence of L-NAME. High co ncentrations of ADP beta S (32 and 100 mu M) and UTP (320 and 1000 mu M) caused contraction of endothelium-denuded preparations. Thus, extra cellular nucleotides cause endothelium-dependent, primarily nitric oxi de-mediated relaxation of human coronary artery. ATP in addition cause s endothelium-independent relaxation. The receptors activated by the n ucleotides appear to be unevenly distributed on the coronary endotheli um. (C) 1998 Elsevier Science B.V. All rights reserved.