title: Direct and reflexive effects of nitric oxide synthase inhibition on blood pressure.
abstract: Direct effects of vasoactive substances on blood pressure can be examined in individuals with tetraplegia due to disruption of descending spinal pathways to sympathetic preganglionic neurons, as cervical lesions interfere with baroreceptor reflex buffering of sympathetic outflow. In this study, we assessed effects of the nitric oxide synthase inhibitor nitro-L-arginine methyl ester (L-NAME) on mean arterial pressure, heart rate, and plasma norepinephrine concentrations in individuals with tetraplegia vs. effects shown in a neurologically intact control group. Seven individuals with tetraplegia and seven age-matched controls received, on separate visits and in the following order, placebo (30 ml normal saline) and 0.5, 1, 2, and 4 mg/kg L-NAME intravenously over 60 min. Supine hemodynamic data were collected, and blood was sampled at the end of each infusion and at 120, 180, and 240 min thereafter. L-NAME increased mean arterial pressure, and the relative increase was greater in the tetraplegia group than in the control group. Heart rate was reduced after L-NAME administration in both groups. L-NAME decreased plasma norepinephrine in the control group but not in the group with tetraplegia. These findings suggest that reflexive sympathoinhibition normally buffers the pressor response to nitric oxide synthase inhibition, an effect that is not evident in individuals with tetraplegia as a result of decentralized sympathetic vasomotor control.
authors.affiliation: Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, 130 West Kingsbridge Rd., Bronx, NY 10468, USA. jm.wecht@va.gov
authors.forename: Jill M
authors.initials: JM
authors.lastname: Wecht
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Weir
authors.forename: David S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: Annmarie
authors.initials: A
authors.lastname: Krothe-Petroff
authors.forename: Ann M
authors.initials: AM
authors.lastname: Spungen
authors.forename: Courtney
authors.initials: C
authors.lastname: Holmes
authors.forename: William A
authors.initials: WA
authors.lastname: Bauman
mesh_terms: D000328:Adult; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009433:Neural Inhibition / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D011782:Quadriplegia / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine