α-MSH and other ACTH fragments improve cardiovascular function and survival in experimental hemorrhagic shock
Abstract
Hypovolemic shock was produced in rats by withdrawing about 50% of the estimated total blood volume. Following mean arterial pressure stabilization in the range of 15-25 mm Hg, with a pulse pressure of 7-12 mm Hg, the rats were given intravenous bolus injections either of ACTH fragments or of saline. The following ACTH fragments or analogs were used: ACTH-(4-10), alpha-MSH, ACTH-(1-16), ACTH-(1-17), ACTH-(1-18), [Nle4,D-Phe7]alpha-MSH, [beta-Ala1,Lys17]ACTH-(1-17)-4-amino-n-butilamide (alsactide). ACTH-(1-24) and human synthetic ACTH-(1-39) were used for comparison. All animals treated with saline died in 22.51 +/- 3.62 min. Treatment with ACTH fragments (160 micrograms/kg i.v.) increased blood pressure and pulse amplitude, the effect starting within a few minutes, gradually increasing, and reaching a maximum in 15-30 min. The blood and pulse pressure increases were sustained, remaining almost stable until the end of the 2 h recording. Two out of nine rats treated with alsactide, which was the least active, died within 2 h after treatment, while all rats treated with the other ACTH fragments or analogs were still surviving at that time. Both on a weight and on a molar basis, the most active was ACTH-(1-24), followed by ACTH-(1-16), by the alpha-MSH analog [Nle4,D-Phe7]ACTH-(1-13), by ACTH-(1-18) and by ACTH-(1-17). The present results show that melanocortins reverse otherwise fatal hypovolemic shock, and suggest a new therapeutic approach for shock treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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Microinjections of α-MSH in the nucleus ambiguus exert excitatory effects on parasympathetic preganglionic neurons via activation of MC4R, resulting in increased vagal input to the heart and bradycardia responses.
“For instance, microinjections of α-MSH in the nucleus ambiguus (nAMB) exerted excitatory effects on parasympathetic preganglionic neurons via activation of MC4R, resulting in increased vagal input to the heart and bradycardia responses [74–76].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [76]
Cites
Opiates and endogenous opioid peptides
Kelly, J. S., & Dingledine, R. J. (1977) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(77)90262-6 · Cited by 1,290 · see citing works
Common precursor to corticotropins and endorphins
Mains, R. E., Eipper, B. A., & LING, N. C. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.7.3014 · Cited by 1,106 · see citing works
Cardiovascular Effects of Endogenous Opiate Systems
Holaday, J. W. (1983) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.23.040183.002545 · Cited by 570 · see citing works
The opiomelanotropinergic neuronal and endocrine systems.
O'Donohue, T., & Dorsa, D. (1982) · Peptides · doi:10.1016/0196-9781(82)90098-5 · Cited by 532 · see citing works
Neuropeptides derived from pro-opiocortin: behavioral, physiological, and neurochemical effects.
de Wied, D., & JOLLES, J. (1982) · Physiological Reviews · doi:10.1152/physrev.1982.62.3.976 · Cited by 493 · see citing works
Central noradrenergic regulation of cerebral blood flow and vascular permeability.
Raichle, M. E., Hartman, B. K., Eichling, J. O., & Sharpe, L. G. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.9.3726 · Cited by 492 · see citing works
Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock
Holaday, J., & Faden, A. (1978) · Nature · doi:10.1038/275450a0 · Cited by 462 · see citing works
Noradrenergic neurons: Morphine inhibition of spontaneous activity
Korf, J., Bunney, B. S., & Aghajanian, G. K. (1974) · European Journal of Pharmacology · doi:10.1016/0014-2999(74)90045-4 · Cited by 434 · see citing works
Sexual Behavior: Pharmacology and Biochemistry
Sandler, M., & Gessa, G. L. (1975) · Medical Entomology and Zoology · Cited by 416 · see citing works
Evidence for two separate opiate peptide neuronal systems
Watson, S., Akil, H., Richard, C. W., & Barchas, J. (1978) · Nature · doi:10.1038/275226a0 · Cited by 410 · see citing works
Goldstein, D. S. (1976) · Elsevier eBooks · doi:10.1016/c2013-0-05741-6 · Cited by 392 · see citing works
COLLIER, H. O. J., & Roy, A. C. (1974) · Nature · doi:10.1038/248024a0 · Cited by 374 · see citing works
Opiate antagonists: a role in the treatment of hypovolemic shock.
Faden, A. I., & Holaday, J. (1979) · Science · doi:10.1126/science.451606 · Cited by 339 · see citing works
Adrenocorticotropin in Rat Brain: Immunocytochemical Localization in Cells and Axons
Watson, S. J., Richard, C. W., & Barchas, J. D. (1978) · Science · doi:10.1126/science.206967 · Cited by 336 · see citing works
ACTH-(1–24) and α-MSH antagonize feeding behavior stimulated by kappa opiate agonists
Poggioli, R., Vergoni, A. V., & Bertolini, A. (1986) · Peptides · doi:10.1016/0196-9781(86)90104-x · Cited by 237 · see citing works
Self-citationJacquet, Y. (1978) · Science · doi:10.1126/science.210506 · Cited by 183 · see citing works
β-Endorphin and male sexual behavior
Meyerson, B. J., & Terenius, L. Y. (1977) · European Journal of Pharmacology · doi:10.1016/0014-2999(77)90359-4 · Cited by 171 · see citing works
β-Endorphin: Possible Involvement in the Antihypertensive Effect of Central α-Receptor Activation
Kunos, G., Farsang, C., & Ramirez-Gonzales, M. D. (1981) · Science · doi:10.1126/science.6108611 · Cited by 164 · see citing works
Interaction between acth fragments, brain opiate receptors and morphine-induced analgesia
Gispen, W. H., Buitelaar, J. K., Wiegant, V. M., et al. (1976) · European Journal of Pharmacology · doi:10.1016/0014-2999(76)90150-3 · Cited by 161 · see citing works
Frederickson, R. C. A., & Norris, F. H. (1976) · Science · doi:10.1126/science.10625 · Cited by 150 · see citing works
Farsang, C., Ramírez-González, M. D., Mucci, L., et al. (1980) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)32152-x · Cited by 146 · see citing works
Lemaire, I. B., Tseng, R., & Lemaire, S. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.12.6240 · Cited by 133 · see citing works
Effect of peptides and amino acids on dihydromorphine binding to the opiate receptor
Terenius, L. Y. (1975) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1975.tb09480.x · Cited by 131 · see citing works
Dunn, A. J., & Kramarcy, N. R. (1984) · Springer eBooks · doi:10.1007/978-1-4615-7178-0_8 · Cited by 120 · see citing works
Akil, H., Hewlett, W. A., Barchas, J. D., & Li, C. H. (1980) · European Journal of Pharmacology · doi:10.1016/0014-2999(80)90363-5 · Cited by 115 · see citing works
Induction of Sexual Excitement by the Action of Adrenocorticotrophic Hormone in Brain
Bertolini, A., Vergoni, W., Gessa, G. L., et al. (1969) · Nature · doi:10.1038/221667a0 · Cited by 112 · see citing works
Self-citationEffect of morphine on synaptosomal Ca++ uptake.
Guerrero-Muñoz, F., Cerreta, K. V., Guerrero, M., et al. (1979) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)31628-9 · Cited by 107 · see citing works
Izquierdo, I., Souza, D. O., Carrasco, M. A., Dias, R. D., Perry, M. L. S., Eisinger, S., Elisabetsky, E., & Vendite, D. (1980) · Psychopharmacology · doi:10.1007/bf00435310 · Cited by 95 · see citing works
THE FALL OF BLOOD PRESSURE CAUSED BY INTRAVENOUS MORPHINE IN THE RAT AND THE CAT
EVANS, A., Nasmyth, P. A., & Stewart, H. C. (1952) · British Journal of Pharmacology and Chemotherapy · doi:10.1111/j.1476-5381.1952.tb00720.x · Cited by 91 · see citing works
Cardiovascular effects of intravenous morphine in the anaesthetized rat
Fennessy, M. R., & Rattray, J. F. (1971) · European Journal of Pharmacology · doi:10.1016/0014-2999(71)90116-6 · Cited by 86 · see citing works
ACTH-induced hyperalgesia in rats
Bertolini, A., Poggioli, R., & Ferrari, W. (1979) · Cellular and Molecular Life Sciences · doi:10.1007/bf01963298 · Cited by 84 · see citing works
Self-citationInteraction of peptides related to ACTH, MSH and β-LPH with neurotransmitters in the brain
Versteeg, D. H. G. (1980) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(80)90041-8 · Cited by 83 · see citing works
ACTH-like neurotropic peptides: possible regulators of rat brain cyclic AMP
Wiegant, V. M., Dunn, A. J., Schotman, P., et al. (1979) · Brain Research · doi:10.1016/0006-8993(79)90310-x · Cited by 81 · see citing works
Corticotropin inhibits food intake in rats
Vergoni, A. V., Poggioli, R., & Bertolini, A. (1986) · Neuropeptides · doi:10.1016/0143-4179(86)90091-0 · Cited by 80 · see citing works
Self-citationACTH-like peptides and morphine: interaction at the level of the CNS
Wiegant, V. M., Gispen, W. H., Terenius, L. Y., & de Wied, D. (1977) · Psychoneuroendocrinology · doi:10.1016/0306-4530(77)90033-6 · Cited by 78 · see citing works
The opioid system and central cardiovascular control: Analysis of controversies
FEUERSTEIN, G. Z. (1985) · Peptides · doi:10.1016/0196-9781(85)90134-2 · Cited by 78 · see citing works
Opioids and neuropeptides: mechanisms in circulatory shock.
Bernton, E. W., Long, J., & Holaday, J. W. (1985) · PubMed · Cited by 76 · see citing works
Cardiovascular effects of peptides related to the enkephalins and β-casomorphin
Wei, E. T., Lee, A., & Chang, J. K. (1980) · Life Sciences · doi:10.1016/0024-3205(80)90275-1 · Cited by 75 · see citing works
Drug Effects on Neuroendocrine Regulation
(1973) · Progress in brain research · doi:10.1016/s0079-6123(08)x6117-5 · Cited by 72 · see citing works
Endorphin-mediated inhibition of locus coeruleus neurons.
Strahlendorf, H., Strahlendorf, J., & Barnes, C. (1980) · Brain Research · doi:10.1016/0006-8993(80)90334-0 · Cited by 72 · see citing works
An inhibitory role of β-endorphin in central cardiovascular regulation
Petty, M. A., de Jong, W., & de Wied, D. (1982) · Life Sciences · doi:10.1016/0024-3205(82)90321-6 · Cited by 66 · see citing works
Effects of ACTH-Like Neuropeptides on Animal Behavior and Man
Bohus, B. (2008) · Pharmacology · doi:10.1159/000137239 · Cited by 62 · see citing works
Moroni, F. (1978) · Neuropharmacology · doi:10.1016/0028-3908(78)90099-0 · Cited by 62 · see citing works
Wood, P. L., Malthe‐Sørenssen, D., Cheney, D. L., & Costa, E. (1978) · Life Sciences · doi:10.1016/0024-3205(78)90490-3 · Cited by 61 · see citing works
Effect of two ACTH-analogs on noradrenaline metabolism in rat brain
Versteeg, D. H. G. (1973) · Brain Research · doi:10.1016/0006-8993(73)90447-2 · Cited by 60 · see citing works
Adrenal-independent, anti-shock effect of ACTH-(1–24) in rats
Bertolini, A., Guarini, S., & Ferrari, W. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90424-3 · Cited by 58 · see citing works
Self-citationNeuropeptides and appetite: contribution of neuropharmacological modeling.
Morley, J. E., Levine, A., Gosnell, B. A., et al. (1984) · PubMed · Cited by 47 · see citing works
Adrenocorticotropin reversal of experimental hemorrhagic shock is antagonized by morphine
Bertolini, A., Guarini, S., Ferrari, W., & Rompianesi, E. (1986) · Life Sciences · doi:10.1016/0024-3205(86)90188-8 · Cited by 46 · see citing works
Self-citationSzalay, K., & Stark, E. (1981) · Life Science · doi:10.1016/0024-3205(81)90679-2 · Cited by 43 · see citing works
Drugs, Neurotransmitters, and Behavior
(1984) · Springer eBooks · doi:10.1007/978-1-4615-7178-0 · Cited by 42 · see citing works
Novales, R. R., Novales, B. J., Zinner, S. H., et al. (1962) · General and Comparative Endocrinology · doi:10.1016/0016-6480(62)90063-1 · Cited by 37 · see citing works
CNS and ACTH-like peptides: neurochemical response and interaction with opiates.
Gispen, W. H., Reith, M. E. A., Schotman, P., et al. (1977) · PubMed · Cited by 36 · see citing works
Collins, J. A. (1969) · Archives of Surgery · doi:10.1001/archsurg.1969.01340160064015 · Cited by 33 · see citing works
Immunocytochemical distribution of corticotropin (ACTH) in monkey brain
Abrams, G., Nilaver, G., Hoffman, D., Zimmerman, E. A., Ferin, M., Krieger, D. T., & Liotta, A. S. (1980) · Neurology · doi:10.1212/wnl.30.10.1106 · Cited by 30 · see citing works
An effect of β-melanocyte stimulating hormone (β-MSH) on α-motoneurones of cat spinal cord
Krivoy, W. A., & Zimmerman, E. (1977) · European Journal of Pharmacology · doi:10.1016/0014-2999(77)90225-4 · Cited by 28 · see citing works
Central sites at which morphine acts when producing cardiovascular effects [proceedings].
Feldberg, W. S., & Wei, E. (1978) · PubMed · Cited by 25 · see citing works
Evidence that melanocortins are physiological antagonists of opioids
Bertolini, A., Poggioli, R., Vergoni, A. V., et al. (1986) · IRIS UNIMORE (University of Modena and Reggio Emilia) · Cited by 25 · see citing works
Self-citationCentral actions of ACTH and related peptides
(1987) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(87)90698-0 · Cited by 25 · see citing works
Comparison of chronic and acute effects of morphine sulfate on cardiovascular function
Pur-Shahriari, A. A., Mills, R. A., Hoppin, F. G., et al. (1967) · The American Journal of Cardiology · doi:10.1016/0002-9149(67)90007-0 · Cited by 22 · see citing works
Effect of proglumide on glycoprotein synthesis in aspirin-induced gastric erosions in rats
Umetsu, T., Kimura, K., Sanai, K., et al. (1980) · European Journal of Pharmacology · doi:10.1016/0014-2999(80)90370-2 · Cited by 21 · see citing works
Endröczi, E. (1977) · PubMed · Cited by 13 · see citing works
ACTH-(1–24) antagonizes the contractile effect of morphine on the isolated rat colon
Castelli, M., Gessa, G. L., & Bertolini, A. (1985) · European Journal of Pharmacology · doi:10.1016/0014-2999(85)90730-7 · Cited by 12 · see citing works
Self-citationACTH INDUCED CHANGES IN THE TRANSMITTERAMINE CONCENTRATION OF INDIVIDUAL BRAIN NUCLEI OF THE RAT
Fekete, M. I. K., Herman, J. P., Palkovits, M., et al. (1976) · Elsevier eBooks · doi:10.1016/b978-0-08-020588-5.50015-1 · Cited by 9 · see citing works
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Targeting melanocortin receptors as a novel strategy to control inflammation
Catania, A., Gatti, S., Colombo, G., & Lipton, J. M. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.1.1 · Cited by 438 · see citing works
Li, S.-J., Varga, K., Archer, P., Hruby, V. J., Sharma, S. D., Kesterson, R. A., Cone, R. D., & Kunos, G. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-16-05182.1996 · Cited by 152 · see citing works
Mioni, C., Bazzani, C., Giuliani, D., Altavilla, D., Leone, S., Ferrari, A., Minutoli, L., Bitto, A., Marini, H., Zaffe, D., et al. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000186762.05301.13 · Cited by 148 · see citing works
Self-citationRetractedGUARINI, S. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.03.029 · Cited by 131 · see citing works
Self-citationMelanocortins and cardiovascular regulation
Versteeg, D. H. G., Van Bergen, P., Adan, R. A. H., & De Wildt, D. J. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00615-3 · Cited by 98 · see citing works
Protective effect of melanocortin peptides in rat myocardial ischemia
Bazzani, C., Guarini, S., Botticelli, A. R., Zaffe, D., Tomasi, A., Bini, A., Cainazzo, M. M., Ferrazza, G., Mioni, C., & Bertolini, A. (2001) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29636-1 · Cited by 59 · see citing works
Self-citationCardiovascular effects of γ-MSH/ACTH-like peptides: structure-activity relationship
Van Bergen, P., Janssen, P. M. L., Hoogerhout, P., De Wildt, D. J., & Versteeg, D. H. G. (1995) · European Journal of Pharmacology · doi:10.1016/0014-2999(95)00657-5 · Cited by 40 · see citing works
Role of the brain melanocortins in blood pressure regulation
do Carmo, J. M., da Silva, A. A., Wang, Z., Fang, T., Aberdein, N., Perez de Lara, C. E., & Hall, J. E. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.03.003 · Cited by 38 · see citing works
Corander, M. P., Fenech, M., & Coll, A. P. (2009) · Circulation · doi:10.1161/circulationaha.109.854612 · Cited by 31 · see citing works
Pavia, J. M., Schiöth, H. B., & Morris, M. J. (2003) · Neuroreport · doi:10.1097/00001756-200304150-00009 · Cited by 25 · see citing works
- Authors
- Bertolini, A., Guarini, S., Rompianesi, E., & Ferrari, W.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Bertolini, Alfio
- ORCID
- Guarini, Salvatore
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 1986-10
- Volume
- 130
- Issue
- 1-2
- Pages
- 19-26
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2041672850
- Cited by
- 96
- References
- 63
- Citations by year
- 2024: 3 · 2022: 1 · 2018: 1 · 2017: 1 · 2015: 1 · 2012: 4
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- alpha-melanocyte-stimulating hormone, ACTH fragments, hypovolemic shock, hemorrhagic shock, melanocortin peptides, blood pressure, survival, shock therapy, ACTH analogs
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Blood Pressure, Female, Hemodynamics, Melanocyte-Stimulating Hormones, Peptide Fragments, Rats, Inbred Strains, Shock, Hemorrhagic, Rats
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