A central nervous system action of nitric oxide in blood pressure regulation
Abstract
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.
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NOS1 activity in the medulla and hypothalamus is important for systemic regulation of blood pressure.
“NOS1 activity in the medulla and hypothalamus is important for systemic regulation of blood pressure [104-107]”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [104]
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“Using perforated patchclamp recording, Li et al. (17) found GABAergic synaptic activity in the PVN neurons was potentiated by NO donors, and the NO-mediated inhibition of firing activity was blocked by the GABA receptor antagonist.”
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Role of Renal Nerves in Mediating the Hypertensive Effects of Nitric Oxide Synthesis Inhibition
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- Authors
- Togashi, H., Sakuma, I., Yoshioka, M., Kobayashi, T., Yasuda, H., Kitabatake, A., Saito, H., Gross, S. S., & Levi, R.
- Affiliations
- Hokkaido University (JP)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1992-07
- Volume
- 262
- Issue
- 1
- Pages
- 343-347
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1953075977
- Cited by
- 270
- References
- 0
- Citations by year
- 2022: 3 · 2021: 6 · 2020: 2 · 2019: 4 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 5
- FWCI
- 10.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Heart, Lung, and Blood Institute (P01HL046403, HL-46403, HL-34215, R01HL034215)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- nitric oxide, blood pressure regulation, L-arginine, central nervous system, sympathetic activity, renal sympathetic nerve activity, pressor response, spinal cord transection, intracisternal administration, neurotransmitter function, vasorelaxation
- MeSH terms
- Animals, Arginine, Blood Pressure, Central Nervous System, Heart Rate, Male, Nitric Oxide, Pressoreceptors, Rats, Inbred Strains, RNA, omega-N-Methylarginine, Rats
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