Correction of regulatory and microcirculatory system disturbances in the early stages of experimental atherosclerosis by synthetic antioxidants

Pozdnyakov, O. M.; Klimenko, E. D.; Kobozeva, L. P.; Michunskaya, A. B.; Смирнов, Л. Д.

doi:10.1007/bf00836401

Cited by 5 publications

(2 citation statements)

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“…There is a correlation between functional state of these systems, microcirculatory disturbances, and the degree of atherosclerotic process in major arteries during hyperlipemia [2,5,8].…”

Section: Abstract: Verapamil; Hypothalamo-pituitary Neurosecretory Smentioning

confidence: 99%

Correction of disturbances in neuroregulatory systems at early stages of atherogenesis with verapamil

et al. 2000

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The effect of verapamil on morphofunctional state of the hypothalamo-pituitary neurosecretory system, adrenergic innervation of microvessels, and microcirculation in the early stages of atherogenesis was studied. Correction of functional aberrations of the neuroregulatory systems and microcirculatory disturbances with verapamil was accompanied by restoration of lipid homeostasis and less pronounced atherosclerotic alterations in major arteries. Key Words: verapamil; hypothalamo-pituitary neurosecretory system; adrenergic innervation of microvessels; atherosclerosisThe hypothalamo-pituitary neurosecretory system (HPNS) and peripheral subdivision of the sympathoadrenal system (SAS), which produce bioactive substances with vasoactive and lipid mobilizing effect (vasopressin, norepinephrine), play an important role in the mechanisms of atherogenesis. There is a correlation between functional state of these systems, microcirculatory disturbances, and the degree of atherosclerotic process in major arteries during hyperlipemia [2,5,8].In view of the priming role of microcirculatory disturbances in the development of polyorgan pathology during hyperlipidemia [4], the search for means of correction of functional disturbances in HPNS and SAS is actual. It was established that some calcium channel blockers affect lipid metabolism and modulate activity of the antioxidant system and SAS [7,10,11]. Calcium blocker verapamil is an active neuroprotector, which protects, in particularly, the neurosecretory pituitary cells [6].Our aim was to study the effect of verapamil on morphofunctional state of the regulatory systems at the early stages of atherogenesis. MATERIALS AND METHODSExperiments were performed on 30 male Chinchilla rabbits weighing 2.5-3.0 kg. Group 1 rabbits (intact controls) were maintained on a standard diet. Group 2 rabbits were given 0.3 g/kg cholesterol during 2 months, which modeled atherogenic diet (ATD) according to N. N. Anichkov. Group 3 rabbits were intramuscularly injected with verapamil (phynoptin, Orion) in a dose of 0.5 mg/kg for 10 days during the 2nd month of the diet. We previously observed marked accumulation of LDL, pronounced changes in HPNS, peripheral subdivision of SAS (adrenergic innervation of microvessels), and microcirculatory vascular bed, and initial lipidosis of the aortal intima after one month of ATD [3,5]. Plasma level of total HDL and LDL fractions were determined. The degree of atherosclerotic process was assessed by the index of atherosclerotic damage (lAD) to the aorta [13]. The hypothalamic supraoptic (SO) nuclei and neurohypophysis were studied on serial brain slices by the methods of Gomori--Maiorova, Nissl, and Milenkov. The functional state of HPNS was assessed as described elsewhere [9] by the content of Gomori-positive substance in neurosecretory cells, hypothalamo-pituitary tract, and posterior pituitary. The percentage of "bright" and

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“…There is a correlation between functional state of these systems, microcirculatory disturbances, and the degree of atherosclerotic process in major arteries during hyperlipemia [2,5,8].…”

Section: Abstract: Verapamil; Hypothalamo-pituitary Neurosecretory Smentioning

confidence: 99%

Correction of disturbances in neuroregulatory systems at early stages of atherogenesis with verapamil

et al. 2000

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“…A correlation has been established between functional state of HHNS during hyperlipoproteinemia and the degree of pathological changes in the microcirculatory bed and major arteries [3,4,6]. The HHNS-produced hormone vasopressin has immunomodulating properties and participates in formation of immunological status [9].…”

Section: Abstract: Thymalin; O:-tocopherol; Atherosclerosis; Neuroenmentioning

confidence: 99%

Effects of thymalin and α-tocopherol on morphofunctional state of neuroendocrine system at the early stages of atherogenesis

et al. 1997

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The effects of thymalin and ~-tocopherol on the morphofunctional state of hypothalamohypophyseal neurosecretory system, thyroid gland, and adrenals at the early stages of atherogenesis are described. Correction of pathological changes in the neuroendocrine organs was accompanied by restoration of lipid homeostasis, decrease in intensity of lipid peroxidation, prevention of progressive atherosclerotic alterations in major arteries. Key Words: thymalin; o:-tocopherol; atherosclerosis; neuroendocrine system; thyroid gland; adrenalsThe hypothalamohypophyseal neurosecretory system (HHNS) is a key component of neuroendocrine regulation of lipid homeostasis [2,10]. A correlation has been established between functional state of HHNS during hyperlipoproteinemia and the degree of pathological changes in the microcirculatory bed and major arteries [3,4,6]. The HHNS-produced hormone vasopressin has immunomodulating properties and participates in formation of immunological status [9]. An important role in pathogenesis of atherosclerosis is played by disorders in the function of endocrine glands [5,8]. The state of neuroendocrine system during hyperlipoproteinemia is most certainly affected by activation of lipid peroxidation and decreased antioxidant activity.We compared the effects of a thymus hormone thymalin and ~-tocopherol on the morphofunctional state of HHNS, thyroid gland, and the adrenals at the early stages of atherogenesis. MATERIALS AND METHODSExperiments were performed on 45 male Chinchilla rabbits weighing 2.5-3.0 kg. Group 1 rabbits (control) Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow were maintained on the standard diet. Group 2 rabbits were given 0.3 g/kg body weight cholesterol during a 2-month period (atherogenic diet model according to N. N. Anichkov). Group 3 rabbits were injected with intramuscular thymalin (0.25 mg/kg) during 10 days on month 2 of the diet. Similarly, group 4 rabbits were injected with ~-tocopherol (50 mg/kg).In serial brain slices the hypothalamic supraoptic (SO) nuclei and neurohypophysis were studied by the methods of Gomori--Maiorova, Nissl, and Milenkov. The functional state of HHNS was accessed according to [7], taking into account the amount of gomori-positive substance in the neurosecretory cells, hypothalamohypophyseal tract and neurohypophysis. The percentage of "bright" and "dark" cells was counted in the SO nuclei, as well as the amount of pyknomorphous cellular elements. The value of neuronal nucleus and soma areas were determined a Leitz-ASM semiautomatic image analyzer. Structural changes in endocrine glands were revealed by staining with hematoxylin and eosin according to Goldman, Mallory, and van Gieson. The mass indices of thyroid and adrenals were determined, and the index of atherosclerotic damage (lAD) to the aorta [1] was used to access the severity of atherosclerotic process. Lipoprotein (LP) fractions and malonic dialdehyde were determined in serum using conventional techniques.

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Correction of hyperlipoproteinogenic microangiopathy and organ pathology with thymalin and leu-enkephalin in the early stages of atherogenesis

et al. 1996

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The effects of thymalin and leu-enkephalin on lipid peroxidation and microcirculatory disorders in the early stages of atherogenesis are compared. Correction of the generalized microcirculatory response to hyperlipoproteinemia with the peptides manifested itself in the regression of atherosclerotic lesions in the aorta and restoration of the morphofunctional state of the myocardium and liver. Key Words: thymalin; leu-enkephalin; hyperlipidemia; microangiopathy; myocardium; liverThe universal nature of the primary microcirculatory response to hyperlipidemia (HLP) indicates that this reaction is a hyperlipoproteinogenic microangiopathy and an obligatory factor in the genesis of organ pathology, including the progression of atherosclerotic changes in organ and major arteries [3][4][5]12]. Previously, HLP correction and inhibition of lipid peroxidation (LPO) was shown to have a positive effect and a relationship was established between the degree of these disorders, on the one hand, and atherosclerotic lesions in organ and major vessels and organ pathology, on the other [8,9,15].Impairment of the immunological status of the organism [6] and of the integral neurotransmitter regulation play an important role in atherogenesis. A polypeptide isolated from the thymus has been used for the correction of neuroimmune processes [1,11]. Endogenous regulatory opioid peptides are involved in the maintenance of homeostasis in different pathologies, specifically, enkephalins have been found to possess a hypolipidemic activity [7,10,14]. We examined the effect of thymalin and leu-enkephalin on lipid metabolism disorders, LPO, microcirculatory disorders, and structural shifts in the target organs in the early stages of atherogenesis. MATERIALS AND METHODSExperiments were performed on 43 male Chinchilla rabbits weighing 2-2.5 kg. Group 1 rabbits (control) were maintained on the standard diet during a 2-month period. Group 2 rabbits were given 0.3 g/kg body weight cholesterol with vegetables (atherogenic diet, ATD) during the same period. Rabbits of groups 3 and 4 received ATD for 1 month and then were injected with thymalin (25 mg/kg) and leu-enkephalin (40 p.g/kg) intramuscularly every day for 10 days of the second month. The animals were sacrificed by air embolism.The state of the microcirculatory bed (MCB) was examined using total film preparations of the intestinal mesentery (the method of V. V. Kupriyanov). The cross-section area of microvessels was determined with an ASM semiautomatic image analyzer (Leitz), and the adrenergic innervation was studied by the method of Falk-Owmen. The intensity of catechola-

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Correction of regulatory and microcirculatory system disturbances in the early stages of experimental atherosclerosis by synthetic antioxidants

Cited by 5 publications

References 1 publication

Correction of disturbances in neuroregulatory systems at early stages of atherogenesis with verapamil

Correction of disturbances in neuroregulatory systems at early stages of atherogenesis with verapamil

Effects of thymalin and α-tocopherol on morphofunctional state of neuroendocrine system at the early stages of atherogenesis

Correction of hyperlipoproteinogenic microangiopathy and organ pathology with thymalin and leu-enkephalin in the early stages of atherogenesis

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