Nitric oxide limits pressor responses to sympathetic activation in rat spinal cord.
N-methyl D-aspartate (NMDA) receptor stimulation is known to activate nitric oxide (NO) synthase, an enzyme present in a high proportion of sympathetic preganglionic neurons. In this study, we have examined the possibility that NO modulates the pressor responses elicited by NMDA receptor stimulation in the spinal cord. In experiments on anesthetized rats, we determined whether intrathecal administration of either 3-morpholinylsydnoneimine chloride (SIN-1), an NO donor, or N:(G)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, affected the response to stimulation of spinal NMDA receptors by NMDA (1 pmol to 1 micromol in 10-microL intrathecal administration). Intrathecal NMDA resulted in dose-dependent increases in blood pressure. SIN-1 (100 nmol) attenuated the pressor responses to NMDA (F(1,70)=12, P=0.001). Conversely, L-NAME (1 nmol to 1 micromol) augmented the pressor response to NMDA in a dose-dependent manner (F(3,161)=28.3, P<0.001). The effect of L-NAME to amplify the pressor response to NMDA was reversed by L-arginine but not by D-arginine. These results indicate that endogenous synthesis of NO in the spinal cord limits the pressor response to stimulation of spinal NMDA receptors.
Arnolda
L F
LF
Cardiovascular Neuroscience Group, Cardiovascular Medicine and Centre for Neuroscience, Flinders University, SA 5042, Australia. Leonard.Arnolda@flinders.edu.au
McKitrick
D J
DJ
Llewellyn-Smith
I J
IJ
Minson
J B
JB
D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; C002385:linsidomine; D016202:N-Methylaspartate; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester