Autoregulatory escape from norepinephrine infusion: roles of adenosine and histamine.
Stimulation of sympathetic fibers or infusion of norepinephrine (NE) into the superior mesenteric artery (SMA) leads to an initial decrease in intestinal blood flow, which is followed by a return of flow toward the base-line value (autoregulatory escape) despite continued nerve stimulation or NE infusion. Although the mechanisms responsible for "autoregulatory escape" have not been defined, accumulation of vasodilator metabolites is frequently invoked to explain this phenomenon. Inasmuch as histamine and adenosine exist in high concentrations in the intestinal mucosa and both are potent vasodilators, we examined the effects of chlorpheniramine (an H1 blocker) and adenosine deaminase (degrades adenosine) on autoregulatory escape from NE infusion. In autoperfused piglet intestinal preparations, we measured SMA blood flow and the arteriovenous oxygen difference during intra-arterial NE infusion before and after blockade with chlorpheniramine or adenosine deaminase. Adenosine deaminase pretreatment increased the peak vasoconstrictor and reduced the steady-state escape responses to NE infusion. Chlorpheniramine did not affect either the vasoconstrictor or escape responses. The oxygen uptake changes induced by NE infusion were not dramatically modified by either treatment. These results indicate that adenosine but not histamine is responsible for at least part of the escape of intestinal blood flow from NE infusion.
D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology*; D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006706:Homeostasis; D007422:Intestines / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology*; D009700:Nucleoside Deaminases / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D002744:Chlorpheniramine; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine; D009638:Norepinephrine