Neurogenically derived nitrosyl factors mediate sympathetic vasodilation in the hindlimb of the rat.
Skeletal muscle vasculature of the hindlimb is innervated by a sympathetic noncholinergic vasodilator system. The aim of this study was to determine whether this vasodilator system may represent postganglionic lumbar sympathetic neurons that synthesize and release nitric oxide (NO) or related NO-containing factors. We examined whether NO synthase (NOS)-positive postganglionic lumbar nerves innervate the hindlimb vasculature of the rat and whether the hindlimb vasodilation produced by electrical stimulation of the lumbar sympathetic chain of anesthetized rats is reduced after the systemic administration of the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI). Subpopulations of lumbar sympathetic cell bodies stained intensely for NOS. Postganglionic fibers and varicosities within the iliac and femoral arteries also stained for NOS. Double ligation of the lumbar chain demonstrated that NOS was transported from the cell bodies toward the peripheral terminals. Low-intensity electrical stimulation of the lumbar chain produced a pronounced hindlimb vasodilation that was markedly diminished by pretreatment with 7-NI (45 mg/kg i.v.). In contrast, the vasodilator potency of acetylcholine and S-nitrosocysteine were augmented by 7-NI. These results suggest that postganglionic lumbar sympathetic neurons may synthesize and release NO-containing factors.
Davisson
R L
RL
Department of Pharmacology, University of Iowa, Iowa City 52242, USA.
Possas
O S
OS
Murphy
S P
SP
Lewis
S J
SJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D005728:Ganglia, Sympathetic / Q000201:enzymology; D006614:Hindlimb / Q000098:blood supply*; D007083:Iliac Artery / Q000294:innervation; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D026403:S-Nitrosothiols; D013564:Sympathetic Nervous System / Q000201:enzymology / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D004791:Enzyme Inhibitors; D007191:Indazoles; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D019001:Nitric Oxide Synthase; D003545:Cysteine; D000109:Acetylcholine; C080122:7-nitroindazole