CORONARY VASOACTIVITY OF ADENOSINE IN THE CONSCIOUS DOG

Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 ± 0.18 (SD) μM and at 1.01 ± 0.25 μM in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique was applied to data on the coronary vasoactivity of 68 adenosine analogs to identify the chemical features of this molecule that determine its vasoactivity. These are: the size of the purine base; the inductive effect of the C-2 substituent; the electron-withdrawing effect of the C-6 substituent; the glycosylic torsion angle; the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and the inductive effect of the C-5' substituent. The hydrophobicity of these analogs did not correlate with vasoactivity, suggesting that the hydrophilicity of the ribose moiety overshadows any hydrophobic influence of the very weakly aromatic purine base.