Role of Nitric Oxide in α-Melanocyte-Stimulating Hormone-Induced Hypotension in the Nucleus Tractus Solitarii of the Spontaneously Hypertensive Rats
Abstract
Pro-opiomelanocortin (POMC) is expressed in the nucleus tractus solitarii (NTS) of the brainstem, where nitric oxide (NO) plays an important role in cardiovascular regulation. The POMC-derived neuropeptides and their receptors are important regulators of energy homeostasis and cardiovascular functions in the central nervous system. In this study, we investigated the cardiovascular effect of alpha-melanocyte-stimulating hormone (alpha-MSH), a POMC-derived neuropeptide, and its relationship with NO pathway in the NTS of spontaneously hypertensive rats (SHR). Unilateral microinjection of alpha-MSH (0.3-300 pmol) into the NTS resulted in a dose-dependent hypotension and bradycardia in urethane-anesthetized SHR. The alpha-MSH-induced hypotension was abolished by pretreatment with the antagonist of melanocortin-3/4 receptor (MC-3/4R), Ac-Nle-c[Asp-His-D-Nal(2')-Arg-Trp-Lys]-NH2 (SHU9119). Blockade of cAMP/protein kinase A (PKA), the downstream effector of melanocortin receptors, by previous injection of N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89) also ablated the cardiovascular effect of alpha-MSH. To elucidate the role of NO pathway in alpha-MSH-evoked hypotension, pretreatment with Nomega-nitro-L-arginine methyl ester, a universal inhibitor of nitric-oxide synthase (NOS), partially reversed the depressor and bradycardic effects of alpha-MSH. Furthermore, previous application of the inducible NOS (iNOS) inhibitor, aminoguanidine, but not the neuronal NOS inhibitor, 7-nitroindazole, attenuated the cardiovascular effect of alpha-MSH. Histological analysis revealed the colocalization of MC-4R, but not MC-3R, with iNOS in the NTS of SHR. In summary, intra-NTS injection of alpha-MSH induces hypotension and bradycardia of SHR via MC-4R signaling, which activates cAMP/PKA and iNOS.
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Microinjections of α-MSH into the dorsal motor nucleus of the vagus complex or the nucleus tractus solitarius lowered blood pressure.
“The acute effects of CNS injections of α-MSH on BP depend on the brain area where it activates its receptors since microinjections of α-MSH into the dorsal motor nucleus of the vagus (DMV) complex or the NTS lowered BP [25, 26] and this response was attenuated by MC4R blockade.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [26]
The blood pressure-lowering response to microinjections of α-MSH into the dorsal motor nucleus of the vagus complex or the nucleus tractus solitarius was attenuated by MC4R blockade.
“The acute effects of CNS injections of α-MSH on BP depend on the brain area where it activates its receptors since microinjections of α-MSH into the dorsal motor nucleus of the vagus (DMV) complex or the NTS lowered BP [25, 26] and this response was attenuated by MC4R blockade.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [26]
The MC4R is a G protein-coupled 7 transmembrane receptor that increases cAMP phosphorylation and activates protein kinase A.
“The MC4R is a G protein-coupled 7 transmembrane receptor that increases cAMP phosphorylation and activates protein kinase A (PKA) [3, 26, 63]; therefore, blockade of these intracellular pathways attenuates MC4R actions [3, 63].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [26]
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- Authors
- Tai, M.-H., Weng, W.-T., Lo, W.-C., Chan, J. Y. H., Lin, C.-J., Lam, H.-C., & Tseng, C.-J.
- Affiliations
- Kaohsiung Medical University (TW)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 321
- Issue
- 2
- Pages
- 455-461
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1996315299
- Cited by
- 24
- References
- 33
- Citations by year
- 2022: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 3 · 2016: 4 · 2014: 2 · 2013: 2
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- alpha-melanocyte-stimulating hormone, nitric oxide, nucleus tractus solitarius, spontaneously hypertensive rats, hypotension, bradycardia, melanocortin-4 receptor, melanocortin 3 receptor, proopiomelanocortin, inducible nitric oxide synthase, cardiovascular regulation
- MeSH terms
- alpha-MSH, Animals, Blood Pressure, Dose-Response Relationship, Drug, Hypertension, Male, Microinjections, Nitric Oxide, Rats, Inbred SHR, Signal Transduction, Solitary Nucleus, Cyclic AMP-Dependent Protein Kinases, NG-Nitroarginine Methyl Ester, Receptor, Melanocortin, Type 4, Cell Line, Tumor, Rats
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