Role of endothelium-derived relaxing factor in the in vivo renal vascular action of adenosine in dogs.
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.
Okumura
M
M
Department of Pharmacology, Osaka City University Medical School, Japan.
Miura
K
K
Yamashita
Y
Y
Yukimura
T
T
Yamamoto
K
K
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
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