A central nervous system action of nitric oxide in blood pressure regulation.
We had reported that the systemic administration of N omega-methyl-L-arginine (L-NMA), a specific inhibitor of nitric oxide (NO) synthesis from L-arginine (ARG), raises arterial blood pressure (BP) while paradoxically enhancing central sympathetic outflow. Cervical spinal cord transection abolishes the increase in sympathetic outflow and attenuates the pressor effect of L-NMA. Thus, in addition to lowering BP by direct vasorelaxation, NO may also act in the central nervous system to reduce vascular sympathetic tone. To test this hypothesis we have injected L-NMA directly into the central nervous system in anesthetized rats. Intracisternally (i.c.), L-NMA elicited a small pressor response accompanied by a marked increase in sympathetic renal nerve activity (RNA). In contrast, the inactive stereoisomer N omega-methyl-D-arginine had neither pressor nor neural effects. The increases in RNA and BP elicited by i.c. L-NMA were abolished by spinal cord transection at C1 to C2 and by the i.v. administration of ARG. When administered i.c., ARG also abolished the increase in RNA elicited by i.v. L-NMA and significantly attenuated the pressor response. Thus, our findings indicate that L-NMA acts centrally by an ARG-reversible mechanism in the anesthetized rat to stimulate sympathetic nerve activity. Inasmuch as centrally synthesized NO has been postulated to play a second messenger and/or neurotransmitter role, our findings suggest that one such function would be the central regulation of sympathetic outflow and hence, BP.
Togashi
H
H
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Sakuma
I
I
Yoshioka
M
M
Kobayashi
T
T
Yasuda
H
H
Kitabatake
A
A
Saito
H
H
Gross
S S
SS
Levi
R
R
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012313:RNA; D001120:Arginine