title: The involvement of endothelium-derived relaxing factor in the regulation of renal cortical blood flow in the rat.
abstract: 1. In the present study the role of endogenous nitric oxide (NO) was investigated, in the regulation of renal cortical blood flow (RCBF) in vivo in anaesthetized rats under conditions in which prostacyclin involvement had been eliminated. 2. Infusions of the NO synthesis inhibitor NG-monomethyl-L-arginine (MeArg) at 1 or 3 mg kg-1 min-1, i.v., produced significant decreases in RCBF of 29 +/- 7% and 35 +/- 5%, respectively. These effects were reversed by co-infusion of a 3 fold excess of L-arginine (L-Arg). 3. Similarly, intravenous infusion of N omega-nitro-L-arginine methyl ester (NO2Arg) at 30 or 300 micrograms kg-1 min-1 attenuated RCBF by 21 +/- 4% or 53 +/- 4%, respectively, and these effects were reversed by L-Arg (3 or 10 mg kg-1 min-1, i.v.). Most importantly, a low dose of NO2Arg (30 micrograms kg-1 min-1, i.v.), while having no pressor effect, considerably reduced RCBF, indicating that basal release of NO is important for the maintenance of renal cortical blood flow. 4. MeArg (3 mg kg-1 min-1, i.v.) or NO2Arg (300 micrograms kg-1 min-1, i.v.) inhibited endothelium-dependent acetylcholine (ACh, 10 micrograms kg-1 min-1, i.v. for 3 min) increases in RCBF in an L-Arg reversible manner, but did not affect endothelium-independent (dopamine 10 micrograms kg-1 min-1, i.v., for 3 min) increases. Endothelin- 1 (1 nmol kg-1, i.v.), when given as a control for the vasoconstrictor effects of MeArg and NO2Arg, produced a slight inhibition of the ACh-induced increase in RCBF, but this effect was significantly weaker than that produced by MeArg or NO2Arg. 5. Our findings suggest that MeArg and NO2Arg inhibit basal and ACh-stimulated release of NO in the renal cortical vasculature. Thus, endogenous NO formation may play an important role in the local regulation of renal cortical blood flow.
authors.affiliation: William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London.
authors.forename: C E
authors.initials: CE
authors.lastname: Walder
authors.forename: C
authors.initials: C
authors.lastname: Thiemermann
authors.forename: J R
authors.initials: JR
authors.lastname: Vane
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007672:Kidney Cortex / Q000098:blood supply* / Q000187:drug effects; D007834:Lasers; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D009609:Nitrous Oxide / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
chemical_list: D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D009609:Nitrous Oxide; D004298:Dopamine; D007213:Indomethacin