Coronary vasoactivity of adenosine in the conscious dog.

Abstract

Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 +/- 0.18 (SD) microns and at 1.01 +/- 0.25 microns 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: (1) the size of the purine base; (2) the inductive effect of C-2 substituent; (3) the electron-withdrawing effect of the C-6 substituent; (4) the glycosylic torsion angle; (5) the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; (7) the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and (8) 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.

Hyaluronidase treatment of coronary glycocalyx increases reactive hyperemia but not adenosine hyperemia in dog hearts

“…Several previous studies in dogs have compared peak coronary hyperemia after occlusion vs. hyperemia induced by intravenous or intracoronary administration of pharmacological agents. These studies have reported similar results between the two interventions (4,19), as well as higher values during RH (9) or higher values with vasodilators (1,11,33). Differences in agents, concentrations, and route of administration seem to underlie the reported disparity.…”

Voltage-dependent K+ channels regulate the duration of reactive hyperemia in the canine coronary circulation

“…For example, Olsson and colleagues (39) performed a kinetic analysis of adenosine washout during reactive hyperemia and suggested that adenosine levels account for coronary flow changes. Additionally, exogenous adenosine (at levels comparable to ischemic production) elicits vasodilation equal to that observed in reactive hyperemia (38). Finally, adenosine deaminase reversibly reduces hyperemic flow (without any effect on peak) following an occlusion longer than 5 s (46).…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…Adenosine is a potent coronary dilator in all species studied, including humans (Cobbin et al, 1974;Olsson et al, 1979;Watt et al, 1987). It can arise directly from cardiomyocytes after intracellular breakdown of ATP and after extracellular breakdown of ATP released from endothelial cells (Pekka Raatikainen et al, 1991).…”