TY - JOUR
T1 - Nitric oxide limits pressor responses to sympathetic activation in rat spinal cord
AU - Arnolda, Leonard F.
AU - McKitrick, Douglas J.
AU - Llewellyn-Smith, Ida J.
AU - Minson, Jane B.
PY - 2000/12
Y1 - 2000/12
N2 - 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 μmol in 10-μL intrathecal administration). Intrathecal NMDA resulted in dose-dependent increases in blood pressure. SIN-1 (100 nmol) attenuated the pressor responses to NMDA (F1,70 = 12, P=0.001). Conversely, L-NAME (1 nmol to 1 μmol) augmented the pressor response to NMDA in a dose-dependent manner (F3,161 = 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.
AB - 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 μmol in 10-μL intrathecal administration). Intrathecal NMDA resulted in dose-dependent increases in blood pressure. SIN-1 (100 nmol) attenuated the pressor responses to NMDA (F1,70 = 12, P=0.001). Conversely, L-NAME (1 nmol to 1 μmol) augmented the pressor response to NMDA in a dose-dependent manner (F3,161 = 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.
KW - Blood pressure
KW - L-NAME
KW - Nitric oxide synthase
KW - Sympathetic nervous system
UR - http://www.scopus.com/inward/record.url?scp=0033664833&partnerID=8YFLogxK
U2 - 10.1161/01.HYP.36.6.1089
DO - 10.1161/01.HYP.36.6.1089
M3 - Article
C2 - 11116130
AN - SCOPUS:0033664833
SN - 0194-911X
VL - 36
SP - 1089
EP - 1092
JO - Hypertension
JF - Hypertension
IS - 6
ER -