Coronary flow increases induced by adenosine and adenine nucleotides are mediated by the coronary endothelium: a new principle of the regulation of coronary flow.

Intracoronary adenosine as well as the adenine nucleotides (ATP, ADP, AMP, beta, gamma-methylene-ATP, diadenosine-tetraphosphate, and polyadenylic acid) do not elicit their dilatory effects directly at the smooth muscle cells of the resistance vessel wall, but indirectly, via the endothelium. This must be concluded, since for these compounds the coronary endothelium represents an impermeable barrier between intra-arterial and intra-capillary spaces on the one hand, and the interstitium on the other. Furthermore, in equimolar concentrations the substances investigated induce quantitatively very similar increases in flow, although they are characterized by a highly differing metabolism during their passage through the coronary system as well as by great differences in molecular weight. These endothelium-dependent reactions cannot be influenced by 10(-4)M methylene blue, 10(-5)M haemoglobin, or pre-perfusion with 10(-6)M indomethacin. Accordingly, neither the EDRF nitric oxide nor PGI2 can be considered to be the mediator of these particular increases. There are now, however, observations indicating that the coronary endothelium and the smooth muscle cells of the coronary resistance vessels act as an electrically communicating 'syncytium'. In the light of these recent discoveries, a new principle of coronary flow regulation is suggested.