A15069 Nanocomposite (Si-ODN-II), containing antisense oligonucleotides targeted to mRNA of the beta-1-adrenoreceptors for hypertension therapy in rats with stress-sensitive arterial hypertension (ISIAH rats)

Abstract

Objectives: The study of the possibility of gene therapy of hypertensive disease using nanocomposite (Si-ODN-II), containing silicon and antisense oligonucleotides directed to mRNA of the beta 1-adrenoreceptors in rats with stress-sensitive hypertension (ISIAH rats). Methods: We used the ISIAH rats, hypertension of which was the result of a severe hereditary predisposition to the development of hypertensive state provoked by emotional stress. PCR real-time revealed enhanced mRNA of Adrb1 receptors in myocardium of the intact ISIAH rats. The inhibition of expression Adrb1 gene was studied using intravenous administration of the Si∼ODN-II antisense nanocomposites. Results: Stimulations of the beta 1-adrenoreceptors cause an increase in the frequency and strength of the heartbeats and are one of the factors in the development of hypertensive disease. Beta-blockers help to slow down the heart rhythm and lower the blood pressure. At the first stage of the work, high expression of the mRNA of the Adrb1 gene in the myocardium in intact ISIAH rats was observed. Further, we investigate the action of the Si ∼ODN-II nanocomposite with antisense ODN to the mRNA of Adrb1 gene on arterial pressure using intravenous administration. Intravenous injection of Si∼ODNI nanocomposite into the ISIAH rats led to a drop in blood pressure of 10–12 mm Hg for four to five days. Conclusion: The study revealed high expression of mRNA Adrb1 in the myocardium of ISIAH rats. Using of Si∼ODN-II nanoparticles with antisense ODN to beta 1-adrenergic receptors by intravenous administration led to a prolonged decrease in arterial pressure in the ISIAH rats, which is an advantage over traditional drugs and has an perspective to be used in clinical practice. The work was supported by the Russian Science Foundation, grant 16–15-10073.