title: Nitric oxide synthase inhibition depresses the height of the cerebral blood flow-pressure autoregulation curve during moderate hypotension.
abstract: Variations in the height of the CBF response to hypotension have been described recently in normal animals. The authors evaluated the effects of nitric oxide synthase (NOS) inhibition on these variations in height using laser Doppler flowmetry in 42 anesthetized (halothane and N2O) male Sprague-Dawley rats prepared with a superfused closed cranial window. In four groups (time control, enantiomer control, NOS inhibition, and reinfusion control) exsanguination to MABPs from 100 to 40 mm Hg was used to produce autoregulatory curves. For each curve the lower limit of autoregulation (the MABP at the first decrease in CBF) was identified; the pattern of autoregulation was classified as "peak" (15% increase in %CBF), "classic" (plateau with a decrease at the lower limit of autoregulation), or "none" (15% decrease in %CBF); and the autoregulatory height as the %CBF at 70 mm Hg (%CBF(70)) was determined. NOS inhibition decreased %CBF(70) in the NOS inhibition group (P = 0.014), in the control (combined time and enantiomer control) group (P = 0.015), and in the reinfusion control group (P = 0.025). NOS inhibition via superfusion depressed the autoregulatory pattern (P = 0.02, McNemar test on changes in autoregulatory pattern) compared with control (P = 0.375). Analysis of covariance showed that changes induced by NOS inhibition in the parameters of autoregulatory height are not related to changes in the lower limit, but are strongly (P < 0.001) related to each other. NOS inhibition depressed the autoregulatory pattern, decreasing the seemingly paradoxical increase in CBF as blood pressure decreases. These results suggest that nitric oxide increases CBF near the lower limit and augments the hypotensive portion of the autoregulatory curve.
authors.affiliation: Department of Anesthesiology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA. sjones@wpahs.org
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jones
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Easley
authors.forename: Carol R
authors.initials: CR
authors.lastname: Radinsky
authors.forename: Douglas
authors.initials: D
authors.lastname: Chyatte
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Furlan
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Perez-Trepichio
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis; D007022:Hypotension; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019335:Nitroarginine; D019001:Nitric Oxide Synthase