Effects of Adenosine and Its Derivatives on the Canine Intestinal Vasculature

The effects of adenosine and two of its structural analogs on small intestinal blood flow, flow distribution, oxygen extraction, and uptake were studied in anesthetized dogs. Adenosine induced dose-dependent increases in intestinal blood flow and oxygen consumption but decreased oxygen extraction. These effects were significantly attenuated by theophylline, an adenosine antagonist. Propranolol did not influence the responses of the intestinal circulation to adenosine suggesting that beta-adrenergic receptors are not involved in the action of adenosine. 2-Chloroadenosine, one of the most potent adenosine analogs, produced changes very similar to adenosine but was about six times more potent on a molar basis. Effects of 2-chloroadenosine were attenuated by a 10-fold smaller dose of theophylline. Adenosine-9 β-d-arabinof uranoside, another analog, was ineffective in the mesenteric circulation. Characteristic activity of both analogs and the antagonism of the effects of adenosine and 2-chloroadenosine by theophylline suggest the presence of adenosine-sensitive binding sites in precapillary resistance vessels of the intestinal circulation. The presence of adenosine receptors in intestinal vascular smooth muscle is further supported by our in vitro results in which all three agents induced patterns of response similar to those noted under in vivo conditions. However, concentrations necessary to obtain relaxation of isolated muscle strips were much greater than those sufficient to produce mesenteric vasodilation in vivo. It was also noted that strips obtained from branches of the superior mesenteric artery were more reactive to adenosine and its analogs were strips prepared from the main trunk of the vessel.