title: Brown Norway rats show impaired nNOS-mediated information transfer in renal autoregulation.
abstract: Nonselective inhibition of NO synthase (NOS) augments myogenic autoregulation of renal blood flow (RBF) and profoundly reduces RBF. Previously in Wistar rats, we showed that augmented autoregulation, but not vasoconstriction, is duplicated by intrarenal inhibition of neuronal NOS (nNOS), whereas intrarenal inhibition of inducible NOS (iNOS) has no effect on RBF or on RBF dynamics. Thus macula densa nNOS transfers information from tubuloglomerular feedback to the afferent arteriole. This information flow requires that macula densa nNOS can sufficiently alter ambient NO concentration, that is, that endothelial NOS (eNOS) and iNOS do not alter local NO concentration. Because the Brown Norway rat often shows exaggerated responses to NOS inhibition and has peculiarities of renal autoregulation that are related to NO, we used this strain to study systemic and renal vascular responses to NOS inhibition. The first experiment showed transient blood pressure reduction by bolus i.v. acetylcholine that was dose-dependent in both strains and substantially prolonged in Brown Norway rats. The depressor response decayed more rapidly after nonselective NOS inhibition and the difference between strains was lost, indicating a greater activity of eNOS in Brown Norway rats. In Brown Norway rats, selective inhibition of iNOS reduced RBF (-16% +/- 7%) and augmented myogenic autoregulation, whereas nNOS inhibition reduced RBF (-25% +/- 4%) and did not augment myogenic autoregulation. The significant responses to intrarenal iNOS inhibition, the reduced modulation of autoregulation by nNOS inhibition, and the enhanced endothelial depressor response suggest that physiological signalling by NO within the kidney is impaired in Brown Norway rats because of irrelevant or inappropriate input of NO by eNOS and iNOS.
authors.affiliation: Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: William A
authors.initials: WA
authors.lastname: Cupples
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006706:Homeostasis; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D012079:Renal Circulation; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D010656:Phenylephrine; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester