Impaired Basal Sympathetic Tone and α1-Adrenergic Responsiveness in Association With the Hypotensive Effect of Melatonin in Spontaneously Hypertensive Rats
Abstract
Early investigations have suggested a relationship between hypertension and melatonin, a pineal hormone. The aims of this study were to evaluate the implication of the sympathetic nervous system in the acute effect of melatonin on blood pressure in conscious 12-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), and to determine whether the hypotensive effect of melatonin is associated with alterations in pre- or postsynaptic mechanisms. Melatonin, 10 mg/kg, produced a sustained time-dependent decrease of mean arterial pressure only in SHR without changes in heart rate in both groups. Until 20 min after melatonin administration, plasma epinephrine (EPI) levels were reduced by about 60% in both groups, but norepinephrine (NE) levels were decreased only in SHR by about 30%. The nitroprusside-induced hypotension responses and the associated increases in heart rate were similar in both groups before or after administration of melatonin. Unexpectedly, the sympathetic reactivity to nitroprusside, evaluated by the increases in NE and EPI, was markedly enhanced after melatonin treatment in both WKY and SHR. The stimulation induced [3H]-norepinephrine release from isolated atria was not altered by melatonin in SHR. In cultured aortic vascular smooth muscle cells, the basal and phenylephrine induced inositol phosphate formations were greater in SHR, and the melatonin pretreatment dose dependently attenuated the phenylephrine responses in cells from both WKY and SHR. Therefore the hypotensive action of melatonin appears to be associated with an inhibition of basal sympathoadrenal tone and could also be mediated partly by the blockade of postsynaptic alpha1-adrenergic receptor-induced inositol phosphate formation.
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Melatonin exhibits beneficial actions on cardiovascular health by enhancing endothelial function, maintaining metabolic homeostasis, and reducing inflammation.
“They also exhibit beneficial actions on cardiovascular health by enhancing endothelial function, maintaining metabolic homeostasis,38 and reducing inflammation.39,40”
From Total and Cause-Specific Mortality of U.S. Nurses Working Rotating Night Shifts (2015) · cites this paper as [38]
Cites
Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine
Peuler, J. D., & Johnson, G. A. (1977) · Life Sciences · doi:10.1016/0024-3205(77)90070-4 · Cited by 1,899 · see citing works
A review of the evidence supporting melatonin's role as an antioxidant
Reiter, R. J., Melchiorri, D., Sewerynek, E., Pöeggeler, B., Barlow‐Walden, L., Chuang, J., Ortíz, G. G., & Acuña-Castroviejo, D. (1995) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1995.tb00133.x · Cited by 816 · see citing works
Melatonin receptors: Are there multiple subtypes?
Dubocovich, M. L. (1995) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)88978-6 · Cited by 409 · see citing works
Menéndez-Peláez, A., & Reiter, R. J. (1993) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1993.tb00511.x · Cited by 351 · see citing works
Gauer, F., Masson‐Pévet, M., Skene, D. J., VIVIEN‐ROELS, B., & Pévet, P. (2008) · Neuroendocrinology · doi:10.1159/000126350 · Cited by 144 · see citing works
Krause, D. N., Barrios, V. E., & DUCKLES, S. P. (1995) · European Journal of Pharmacology · doi:10.1016/0014-2999(95)00028-j · Cited by 111 · see citing works
Melatonin Decreases Brain Serotonin Release, Arterial Pressure and Heart Rate in Rats
Chuang, J. I., Chen, S. S., & Lin, M. T. (2008) · Pharmacology · doi:10.1159/000139083 · Cited by 99 · see citing works
Experimental hypertension in pinealectomized rats
Zanoboni, A., & Zanoboni-Muciaccia, W. (1967) · Life Sciences · doi:10.1016/0024-3205(67)90043-4 · Cited by 77 · see citing works
Antihypertensive Action of Melatonin in the Spontaneously Hypertensive Rat
Kawashima, K., Miwa, Y., Fujimoto, K., Oohata, H., Nishino, H., & Koike, H. (1987) · Clinical and Experimental Hypertension. Part A: Theory and Practice · doi:10.3109/10641968709160037 · Cited by 75 · see citing works
Zisapel, N., Egozi, Y., & Laudon, M. (2008) · Neuroendocrinology · doi:10.1159/000124062 · Cited by 68 · see citing works
Laitinen, J. T., Viswanathan, M. N., Vakkuri, O., et al. (1992) · Endocrinology · doi:10.1210/endo.130.4.1312446 · Cited by 50 · see citing works
Laflamme, A. K., Oster, L., Cardinal, R., et al. (1997) · Hypertension · doi:10.1161/01.hyp.30.2.278 · Cited by 44 · see citing works
Studies with Pinealectomized Rats
Karppanen, H., Vapaatalo, H., Lahovaara, S., et al. (2008) · Pharmacology · doi:10.1159/000136065 · Cited by 42 · see citing works
Melatonin in Serum and the Pineal of Spontaneously Hypertensive Rats
Kawashima, K., Nagakura, A., Wurzburger, R. J., et al. (1984) · Clinical and Experimental Hypertension · doi:10.3109/10641968409044066 · Cited by 41 · see citing works
Differential Expression of Melatonin Receptors in Spontaneously Hypertensive Rats
Viswanathan, M. N., Laitinen, J. T., & Saavedra, J. M. (2008) · Neuroendocrinology · doi:10.1159/000126318 · Cited by 38 · see citing works
Wu, L., & de Champlain, J. (1996) · Journal of Hypertension · doi:10.1097/00004872-199605000-00008 · Cited by 35 · see citing works
Karppanen, H., Mm, A., & Särkimäki, I. (1973) · PubMed · Cited by 35 · see citing works
Wu, L., Wang, R. T., & de Champlain, J. (1998) · Journal of Hypertension · doi:10.1097/00004872-199816030-00011 · Cited by 26 · see citing works
Yasin, S. A., Grossman, A. B., & Forsling, M. L. (1996) · Brain Research Bulletin · doi:10.1016/0361-9230(95)02024-1 · Cited by 25 · see citing works
Borkowski, K. R. (1991) · Journal of Autonomic Pharmacology · doi:10.1111/j.1474-8673.1991.tb00239.x · Cited by 25 · see citing works
Foucart, S. (1996) · American Journal of Hypertension · doi:10.1016/0895-7061(95)00297-9 · Cited by 20 · see citing works
Effects of an Aldosterone Antagonist, Spironolactone, on Pinealectomized Rats
Karppanen, H., & Vapaatalo, H. (2008) · Pharmacology · doi:10.1159/000136251 · Cited by 10 · see citing works
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Gu, F., Han, J., Laden, F., Pan, A., Caporaso, N. E., Stampfer, M. J., Kawachi, I., Rexrode, K. M., Willett, W. C., Hankinson, S. E., et al. (2015) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2014.10.018 · Cited by 202 · see citing works
Prolonged melatonin administration decreases nocturnal blood pressure in women
CAGNACCI, A., CANNOLETTA, M., RENZI, A., BALDASSARI, F., ARANGINO, S., & VOLPE, A. (2005) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2005.05.008 · Cited by 156 · see citing works
Fabbian, F., Smolensky, M. H., Tiseo, R., Pala, M., Manfredini, R., & Portaluppi, F. (2013) · Chronobiology International · doi:10.3109/07420528.2012.715872 · Cited by 147 · see citing works
Melatonin improves memory acquisition under stress independent of stress hormone release
Rimmele, U., Spillmann, M., Bärtschi, C., Wolf, O. T., Weber, C. S., Ehlert, U., & Wirtz, P. H. (2009) · Psychopharmacology · doi:10.1007/s00213-008-1344-z · Cited by 46 · see citing works
Melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans
Ray, C. A. (2003) · The Journal of Physiology · doi:10.1111/j.1469-7793.2003.01043.x · Cited by 51 · see citing works
- Authors
- K.-Laflamme, A.
- Venue
- American Journal of Hypertension
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-02
- Volume
- 11
- Issue
- 2
- Pages
- 219-229
- ISSN
- 0895-7061 (ISSN-L)
- OpenAlex
- W2127354161
- Cited by
- 97
- References
- 22
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 8 · 2015: 6 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- melatonin, hypertension, spontaneously hypertensive rats, sympathetic nervous system, alpha1-adrenoceptors, norepinephrine, epinephrine, inositol phosphate formation, vascular smooth muscle, blood pressure
- MeSH terms
- Animals, Blood Pressure, Catecholamines, Heart Rate, Hypertension, Male, Melatonin, Norepinephrine, Phosphatidylinositols, Rats, Inbred SHR, Rats, Inbred WKY, Reflex, Sympathetic Nervous System, Receptors, Adrenergic, alpha-1, Rats
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