title: The role of adenosine in HgCl2-induced acute renal failure in rats.
abstract: It has been proposed that adenosine mediates the renal hemodynamic changes in acute renal failure (ARF) and that these changes are pathogenic in reducing glomerular filtration rate. Consistently, adenosine-receptor antagonists such as theophylline have been shown to have protective effects in several experimental models of ARF. The present experiments were designed to explore the potential role of adenosine in HgCl2-induced ARF in rats. In isolated perfused rat kidneys, HgCl2 increased adenosine production and induced a concentration-dependent vasoconstriction. However, the vasoconstriction was unrelated to adenosine production and was not antagonized by theophylline. During the initiation phase of HgCl2-induced ARF in intact rats (first 4 h after injection), theophylline failed to reverse the reduction in inulin clearance, and this failure could not be attributed to a loss of vascular responsiveness to adenosine, since N6-cyclohexyladenosine, a receptor agonist, produced a further reduction in inulin clearance. Furthermore, theophylline actually had deleterious effects during the maintenance phase of HgCl2-induced ARF in intact unanesthetized rats, as evidenced by higher mean serum creatinine values in theophylline-injected rather than in saline-injected rats, on both the second and third days after HgCl2 injection. Therefore HgCl2 acutely increases renal adenosine production, but increased adenosine does not mediate acute HgCl2-induced renal vasoconstriction, and adenosine-receptor antagonism does not have protective effects during the initiation or the maintenance phases of HgCl2-induced ARF in rats. These results provide no support for the hypothesis that increased adenosine mediates the hemodynamic changes in HgCl2-induced ARF.
authors.affiliation: Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
authors.forename: N
authors.initials: N
authors.lastname: Rossi
authors.forename: V
authors.initials: V
authors.lastname: Ellis
authors.forename: T
authors.initials: T
authors.lastname: Kontry
authors.forename: S
authors.initials: S
authors.lastname: Gunther
authors.forename: P
authors.initials: P
authors.lastname: Churchill
authors.forename: A
authors.initials: A
authors.lastname: Bidani
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000241:Adenosine / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008627:Mercuric Chloride / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D013806:Theophylline / Q000494:pharmacology
chemical_list: D008627:Mercuric Chloride; D013806:Theophylline; D000241:Adenosine