We propose an original method for controlling BP by administration of Si~ODN nanocomposites containing antisense oligonucleotides fixed on silicon-organic nanoparticles. ODN in nanocomposites are targeted to mRNA of the genes encoding angiotensin-converting enzyme (ACE1) and type 1 angiotensin-II receptor (AT1A). The experiments were performed on hypertensive ISIAH rats, a genetic model of hypertension. Single inhalation or intraperitoneal administration of the nanocomposites targeted to ACE1 mRNA or ATA1 mRNA, respectively, led to a pronounced decrease (by ~30 mm Hg) in systolic BP in ISIAH rats over a week. The use of scrambled ODN in the nanocomposites had no effect. A decrease in the expression of ACE1 and AT1A genes under the effect of the corresponding antisense ODN was demonstrated, which attested to directed effect of the test preparations.
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Abramova TO, Ryazanova MA, Antonov EV, Redina OE, Markel AL. Increase in the concentration of SEH protein in renal medulla of ISIAH rats with inherited stress-induced arterial hypertension. Mol. Biol. (Mosk). 2017;51(3):442-446.
Chattopadhyay N, Kher R, Godbole M. Inexpensive SDS/phenol method for RNA extraction from tissues. Biotechniques 1993;15(1):24-26.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.
Kintsurashvili E, Gavras I, Johns C, Gavras H. Effects of antisense oligodeoxynucleotide targeting of the alpha(2B)-adrenergic receptor messenger RNA in the central nervous system. Hypertension 2001;38(5):1075-1080.
Levina AS, Repkova MN, Shikina NV, Ismagilov ZR, Yashnik SA, Semenov DV, Savinovskaya YI, Mazurkova NA, Pyshnaya IA, Zarytova VF. Non-agglomerated silicon-organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties. Beilstein J. Nanotechnol. 2018;9:2516-2525.
Liberman A, Mendez N, Trogler WC, Kummel AC. Synthesis and surface functionalization of silica nanoparticles for nanomedicine. Surf. Sci. Rep. 2014;69(2-3):132-158.
Markel AL, Maslova LN, Shishkina GT, Mahanova NA, Jacobson GS. Developmental influences on blood pressure regulation in ISIAH rats. Development of the hypertensive phenotype, basic and clinical studies. In the series Handbook of Hypertension. McCarty R, Blizard DA, Chevalier RL, eds. Amsterdam, 1999. P. 93-526.
Morishita R, Gibbons GH, Tomita N, Zhang L, Kaneda Y, Ogihara T, Dzau VJ. Antisense oligodeoxynucleotide inhibition of vascular angiotensin-converting enzyme expression attenuates neointimal formation: evidence for tissue angiotensin-converting enzyme function. Arterioscler. Thromb. Vasc. Biol. 2000;20(4):915-922.
Repkova MN, Levina AS, Seryapina AA, Shikina NV, Bessudnova EV, Zarytova VF, Markel AL. Toward gene therapy of hypertension: experimental study on hypertensive ISIAH rats. Biochemistry (Mosc). 2017;82(4):454-457.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 1, pp. 125-128, January, 2019
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Levina, A.S., Repkova, M.N., Klimov, L.O. et al. Antisense Oligonucleotides Immobilized on Silicon-Organic Nanoparticles as a Tool for Prolonged Correction of Hypertensive States. Bull Exp Biol Med 167, 116–119 (2019). https://doi.org/10.1007/s10517-019-04473-5
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DOI: https://doi.org/10.1007/s10517-019-04473-5