Renal vasodilation to histamine in vitro: roles of nitric oxide, cyclo-oxygenase products and H2 receptors.
The aim of this study was to evaluate the roles of nitric oxide (NO) and prostanoids in vasodilation to histamine in the preconstricted isolated perfused rat kidney. Kidneys were excised from Hypnorm/Hypnovel-anaesthetised Wistar rats and perfused at constant flow in vitro. Renal perfusion pressure was elevated similarly with methoxamine (3 microM) or modified Krebs Henseleit solution containing high KCl (30 mM) and vasodilation to histamine (10, 30 nmol) and papaverine (30, 100 nmol) was then examined before and during perfusion with the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.3 mM) or the cyclo-oxygenase inhibitor, indomethacin (10 microM). Furthermore, the vasodilator response to 30 nmol histamine was examined in the presence of the H2 receptor antagonist, ranitidine (0.1-10 microM). Vasodilation to histamine (10, 30 nmol) was found to be unaffected by L-NAME (0.3 mM) or indomethacin (10 microM), while ranitidine (0.1-10 microM) antagonised vasodilation to 30 nmol histamine with an estimated pA2 of 6.67. Vasodilation to histamine in the isolated perfused rat kidney is therefore probably independent of NO and prostanoids and mediated by H2 receptors.
Laight
D W
DW
Pharmacology Group, Bath University, Claverton Down.
Woodward
B
B
Waterfall
J F
JF
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D011970:Receptors, Histamine H2; D009569:Nitric Oxide; D011189:Potassium Chloride; D006632:Histamine; D011899:Ranitidine; D001120:Arginine; D010208:Papaverine; D011451:Prostaglandin-Endoperoxide Synthases; D008729:Methoxamine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin