心臓血管薬理学: オープンアクセス

概要

Hypertrophic and Inflammatory Markers in Isoproterenol-Induced CardiacHypertrophy and its Pharmacological Correction

Sukoyan GV*, Golovach SV, Dolidze NM, Kezeli TD, Gongadze NV, Chipashvili M and Okujava MV

Backgrounds: Short-term sustained beta-adrenergic stimulation is a hallmark of sympathetic hyperactivity and a common future in cardiovascular disease. Activation of endogenous cell signaling pathways that negatively regulate cardiac hypertrophy including the decline of NAD and the reduction of the intracellular NAD+/NADH ratio. The hypothesis that prevention of NAD depletion in myocardium may be critical in the treatment of cardiac hypertrophy and inflammatory responses was tested.

Methods: On the 7 days of isoproterenol (ISO)-induced cardiac hypertrophy (CH) all animals were randomly assigned into 3 groups: control-without therapy (infusion of 0,9% NaCl); main I-receive 10 mg/kg nebivolol per os in combination with lisinopril infusion; and main II-receive infusion of 15 mg/kg of Nadcin® dissolved in water for injection. All animals were euthanized throughout 7 days after beginning of treatment.

Results and conclusion: The increases of heart weight by 18,6% and heart-to-body weight ratio by 35,5% observed in ISO-induced CH were significantly suppressed in lisinopril-nebivolol therapy and monotherapy with NAD+- containing drug, Nadcin®. Therapy with Nadcin® restored the normal level of NAD+/NADH ratio and norepinephrine, in myocardium and cerebral arteries, decrease level of nuclear factor kappa B (NF-kB) and tumor necrosis factor (TNF)- alpha in myocardium, cerebral arteries and blood and as a result blocking the myocardial hypertrophy progression. Treatment with Nadcin® on the ISO-induced model of cardiac injury in rabbits occurs significant anti-hypertrophic and anti-inflammatory effects and occurs preventive action on the redox-potential, NAD+/NADH decreasing and NAD+ depletion of myocardium and redox-potential decreasing in cerebral arteries. Thus, therapeutic strategy for NAD repletion have shown high therapeutic potential for cardiac, vascular and neurologic diseases.