title: Endogenous nitric oxide derived from NOS I or II in thoracic spinal cord exerts opposing tonic modulation on sympathetic vasomotor tone via disparate mechanisms in anesthetized rats.
abstract: The sympathetic preganglionic neurons (SPN) in the thoracic spinal cord regulate vasomotor tone via norepinephrine released from sympathetic terminals and adrenal medulla. We assessed the hypothesis that nitric oxide synthase I (NOS I)- and NOS II-derived nitric oxide (NO) in the thoracic spinal cord differentially modulate sympathetic outflow and that the adrenal medulla may be involved in those modulatory actions. In Sprague-Dawley rats, NOS I immunoreactivity was distributed primarily in the perikaryon, proximal dendrites, or axons of SPN, and small clusters of NOS II immunoreactivity impinged mainly on the circumference of SPN. Intrathecal administration of 7-nitroindazole (7-NI), a specific NOS I antagonist, into the thoracic spinal cord significantly reduced arterial pressure, heart rate, and basal or baroreflex-mediated sympathetic vasomotor tone. On the other hand, intrathecal application of S-methylisothiourea (SMT), a specific NOS II antagonist, elevated arterial pressure with a transient reduction of heart rate, induced a surge of plasma norepinephrine, and reduced baroreflex-mediated but not basal sympathetic vasomotor tone. Bilateral adrenalectomy significantly exacerbated the cardiovascular responses to 7-NI but antagonized those to SMT. We conclude that both NOS I and NOS II are present in the thoracic spinal cord and are tonically active under physiological conditions. Furthermore, the endogenous NO generated by NOS I-containing SPN exerts a tonic excitatory action on vasomotor tone mediated by norepinephrine released from the adrenal medulla and sympathetic nerve terminals. On the other hand, NO derived from NOS II exerts a tonic inhibitory action on sympathetic outflow from the SPN that targets primarily the blood vessels.
authors.affiliation: Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China;
authors.forename: Yan-Yuen
authors.initials: YY
authors.lastname: Poon
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China;
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; and.
authors.forename: Chung-Dar
authors.initials: CD
authors.lastname: Cheng
authors.affiliation: Institute of Physiology, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors.forename: Alice Y W
authors.initials: AY
authors.lastname: Chang
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China; shhchan@adm.cgmh.org.tw.
authors.forename: Samuel H H
authors.initials: SH
authors.lastname: Chan
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D001369:Axons; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001808:Blood Vessels / Q000378:metabolism / Q000502:physiology; D003712:Dendrites; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009474:Neurons; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013904:Thoracic Vertebrae; D014666:Vasomotor System / Q000378:metabolism* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D007550:Isothiuronium; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C027744:S-methylisothiopseudouronium; C080122:7-nitroindazole; D009638:Norepinephrine
keywords: adrenal medulla; blood pressure; norepinephrine; sympathetic preganglionic neurons; vasomotor tone