Effects of adenosine, an adenosine-A1 antagonist, and their combination in splanchnic occlusion shock in rats.
Splanchnic artery occlusion (SAO) with reperfusion results in a severe form of circulatory shock. To study the possible involvement of adenosine in this shock state, we have examined the effects of adenosine, an adenosine A1-receptor antagonist, and their combination in a rat model of SAO shock. Pentobarbital-anesthetized rats were subjected to a 90-min occlusion of both the celiac and superior mesenteric arteries followed by reperfusion. Rats given only the vehicle for adenosine (i.e., 0.9% NaCl) developed severe hypotension following reperfusion, and the survival rate was less than 30% 2 hr after reperfusion. Final plasma free amino-nitrogen concentrations, cathepsin D and myocardial depressant factor (MDF) activities were significantly elevated in rats receiving only the vehicle. Infusion of adenosine (i.e., 30 micrograms/kg/min, i.v.), starting 45 min postocclusion, did not significantly improve the survival rate but did attenuate the accumulation of MDF. Eighty percent (i.e., 4 of 5) rats given KF15372, an adenosine A1-antagonist, 45 min postocclusion (500 micrograms/kg), survived 2 hr. KF15372 also attenuated the increased plasma free amino-nitrogen and MDF. Seventy-five percent (i.e., 6 of 8) rats treated with KF15372 and adenosine survived 2 hr. This combined treatment significantly attenuated the increased plasma levels of free amino-nitrogen, cathepsin D, and MDF. These results suggest that endogenous adenosine plays a significant role in the pathogenesis of shock following SAO and reperfusion, and that blockade of the adenosine A1-receptor could be beneficial in shock states.
Karasawa
A
A
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Rochester
J A
JA
Lefer
A M
AM
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002402:Cathepsin D / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D009201:Myocardial Depressant Factor / Q000097:blood / Q000187:drug effects; D058914:Purinergic Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion; D013152:Splanchnic Circulation; D014970:Xanthines / Q000494:pharmacology*
D009201:Myocardial Depressant Factor; D058914:Purinergic Antagonists; D014970:Xanthines; C067197:8-(dicyclopropylmethyl)-1,3-dipropylxanthine; D002402:Cathepsin D; D000241:Adenosine