title: The role of nitric oxide in the development of neurogenic pulmonary edema in spinal cord-injured rats: the effect of preventive interventions.
abstract: Neurogenic pulmonary edema (NPE) is an acute life-threatening complication following an injury of the spinal cord or brain, which is associated with sympathetic hyperactivity. The role of nitric oxide (NO) in NPE development in rats subjected to balloon compression of the spinal cord has not yet been examined. We, therefore, pretreated Wistar rats with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) either acutely (just before the injury) or chronically (for 4 wk prior to the injury). Acute (but not chronic) L-NAME administration enhanced NPE severity in rats anesthetized with 1.5% isoflurane, leading to the death of 83% of the animals within 10 min after injury. Pretreatment with either the ganglionic blocker pentolinium (to reduce blood pressure rise) or the muscarinic receptor blocker atropine (to lessen heart rate decrease) prevented or attenuated NPE development in these rats. We did not observe any therapeutic effects of atropine administered 2 min after spinal cord compression. Our data indicate that NPE development is dependent upon a marked decrease of heart rate under the conditions of high blood pressure elicited by the activation of the sympathetic nervous system. These hemodynamic alterations are especially pronounced in rats subjected to acute NO synthase inhibition. In conclusion, nitric oxide has a partial protective effect on NPE development because it attenuates sympathetic vasoconstriction and consequent baroreflex-induced bradycardia following spinal cord injury.
authors.affiliation: Institute of Experimental Medicine and Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. jirisedy@hotmail.com
authors.forename: Jirí
authors.initials: J
authors.lastname: Sedy
authors.forename: Josef
authors.initials: J
authors.lastname: Zicha
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kunes
authors.forename: Ales
authors.initials: A
authors.lastname: Hejcl
authors.forename: Eva
authors.initials: E
authors.lastname: Syková
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity; D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure; D001919:Bradycardia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005730:Ganglionic Blockers / Q000008:administration & dosage; D006339:Heart Rate; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007530:Isoflurane / Q000633:toxicity; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010425:Pentolinium Tartrate / Q000008:administration & dosage; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013997:Time Factors; D014661:Vasoconstriction
chemical_list: D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D018727:Muscarinic Antagonists; D009569:Nitric Oxide; D001285:Atropine; D010425:Pentolinium Tartrate; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester