title: Role of endothelium-derived relaxing factor in the in vivo renal vascular action of adenosine in dogs.
abstract: Intrarenal infusion of adenosine induces transient renal vasoconstriction followed by sustained renal vasodilation. The purpose of this study was to elucidate the role of endothelium-derived relaxing factor (EDRF) in renal hemodynamic actions of adenosine in anesthetized dogs. Intrarenal arterial infusion (i.r.a.) of EDRF synthesis inhibitors, L-NG-monomethyl-arginine (160 micrograms/kg/min) and L-NG-nitro-arginine (80 micrograms/kg/min), attenuated acetylcholine-induced increases in renal blood flow and renal vascular resistance was increased. Renal vasoconstriction elicited by adenosine (100 nmol/min i.r.a.) was potentiated and the duration was prolonged by pretreatment with either EDRF synthesis inhibitor. Adenosine infusion significantly decreased glomerular filtration rate (GFR) by more than 30% in the presence of EDRF inhibitors, whereas GFR remained unchanged by adenosine in the absence of EDRF synthesis inhibitors. L-arginine (2 mg/kg/min i.r.a.) significantly reversed the potentiation of adenosine-induced renal vasoconstriction and adenosine-induced reduction in GFR elicited by pretreatment with EDRF synthesis inhibitors. On the other hand, the adenosine A2 selective agonist, CGS 21680C (0.37 nmol/kg/min i.r.a), elicited monophasic renal vasodilation and this effect on renal blood flow was unaffected by EDRF inhibitor. These results suggest that arginine-derived EDRF is involved in the renal vascular action of adenosine. In the present experimental setting, we obtained no evidence for the interaction between arginine-derived EDRF and CGS 21680C-activated A2 adenosine receptor in renal vascular beds.
authors.affiliation: Department of Pharmacology, Osaka City University Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okumura
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Yukimura
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010627:Phenethylamines / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D010627:Phenethylamines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C031433:8-(4-sulfophenyl)theophylline; D001120:Arginine; D013806:Theophylline; D000241:Adenosine; D000109:Acetylcholine