Method for endothelial dysfunction correction by solution of homoeopathic dilutions of human endothelial nitrogen oxide synthase antibodies in complex with solution of homoeopathic dilutions of angiotensin ii receptor c-terminal fragment antibodies

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to experimental cardiology, and concerns the L-NAME-induced endothelial dysfunction correction. That is ensured by introducing the mixture of solutions of homoeopathic dilutions of rabbit monoclonal antibodies to human endothelial nitrogen oxide synthase C12, C30, C200 (9 ml/kg/day) in complex with the mixture of solutions of homoeopathic dilutions of angiotensin II receptor C-terminal fragment antibodies C12, C30, C200 in a dose of 9 ml/kg/day.

EFFECT: method provides the effective endothelial dysfunction correction in the specific experimental environment.

1 tbl

 

The invention relates to medicine, in particular to the experimental cardiovascolari, and can be used for the correction of L-Name-induced endothelial dysfunction.

The prior art method of correction of endothelial dysfunction with a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person - C12, C30, C200, described in the patent of the Russian Federation No. 2306953 C1 (AK 39/395, 27.09.2007,).

The disadvantage of this method is that the main mechanism of action of a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide - C12, C30, C200 is an increase of eNOS, which limits its effectiveness.

The objective of the invention is to increase the efficiency of correction of endothelial dysfunction mixture as by increasing the number of samples, and by eliminating the effects of angiotensin II.

The solution of this problem is provided by the fact that the background modeling L-name-induced endothelial dysfunction in the experiment intraperitoneal introduction of laboratory animal within 28 days of the blocker of NO synthesis L-nitro-arginine-methyl ester (L-NAME) at a dose of 12.5 mg/kg/day., is its correction by the introduction of a mixture of solutions of homeopathic dilutions of polyclonal rabbit and the antibodies to endothelial synthase nitric oxide person - C12, C30, C200 (intragastric, 2 times daily 4.5 ml/kg (9 ml/kg/day.)) in combination with a mixture of solutions of homeopathic dilutions of antibodies to C-terminal fragment of the receptor of angiotensin II-C12, C30, C200, intragastric, 2 times daily 4.5 ml/kg (9 ml/kg/day).

The use of the inventive method a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide - C12, C30, C200, in combination with a mixture of solutions of homeopathic dilutions of antibodies to C-terminal fragment of the receptor of angiotensin II - C12, C30, C200 leads not only to increase the number of samples but also to blockade angiotensinogen receptor type 1 and eliminate such effects of angiotensin II, such as: conversion of nitric oxide in peroxynitrate, stimulation of the synthesis of endothelin, stimulation of the production of cytokines and the initiation thereby inflammation in the vascular wall, hyperactivation of the renin-angiotensin aldosterone system (RAAS)leading to the formation of endothelial dysfunction.

The claimed method can be carried out as follows.

Experiments carried out on white rats male Wistar weighing 250-300 g N-nitro-L-arginine methyl ester (L-NAME) is injected intraperitoneally at a dose of 12.5 mg/kg/day. On the 29th day from the beginning of the experiment under General anesthesia (sodium thiopental (50 mg/kg) catheter in the left carotid artery to register showing the indices of blood pressure (BP), a bolus of pharmacological agents in the right femoral vein. Hemodynamic parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) was measured continuously by a sensor TSD104A and hardware-software complex MR, production Biopac System, Inc., USA. Functional tests: endothelium-dependent vasodilatation (ESV) - intravenous administration of acetylcholine (ach) at a dose of 40 mcg/kg, endothelium-independent vasodilatation (ANSW) - intravenous sodium nitroprusside (NP) at a dose of 30 µg/kg

The degree of development of endothelial dysfunction assessed by the coefficient of endothelial dysfunction (QED), which is the ratio of the area of the triangle above the trend of the reduction reaction of blood pressure (BP) in response to the introduction of sodium nitroprusside (NP), while the points of the smaller leg is the point of maximum fall AD and point out the AD on the plateau with the introduction of functional tests with the introduction of the NP to the area of the triangle above the trend of the reduction reaction of blood pressure in response to the introduction acetylcholine (ach), and for the shorter of the legs take the difference between the end point of cardiac component and a recovery point HELL with the introduction of functional tests with the introduction of OH, and great legs in those treuga what the lights are indicators of recovery time vascular reactions to the introduction of AH and TM, expressed in seconds; area calculated triangles is expressed in arbitrary units (see, for example, a known method described in patent RU 2301015).

When the statistical processing of the data was calculated the mean value, the standard deviation value. The differences were considered significant at p<0,05.

Processing of experimental data when carrying out functional tests on endothelium-dependent (acetylcholine 40 µg/kg) and endothelium-independent (nitroprusside 30 mg/kg/in) relaxation of blood vessels in experimental animals have found that intraperitoneal injection of L-Name at a dose of 12.5 mg/kg for 28 days caused an increase of the coefficient of endothelial dysfunction to 3.5±0.5 srvc. units (table 1), whereas in the control group of animals (intragastric administration of distilled water at a dose of 9 ml/kg/day), it was 1.2±0.1 srvc. units

In the group of animals, where the infusion of L-NAME at a dose of 12.5 mg/kg for 28 days were intragastrically administered a mixture of solutions of homeopathic dilution of polyclonal rabbit antibodies to endothelial synthase oksida nitrogen person, at a dose of 9 ml/kg - C12, C30, C200 QED amounted to 1.8±0.1 srvc. units

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Table 1
Dynamics HELL and ratios are the NTA endothelial dysfunction in the simulation of L-Name-induced endothelial dysfunction and correct it with a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial oxide synthase nitrogen person, at a dose of 9 ml/kg - C12, C30, C200 in complex with a mixture of solutions of homeopathic dilutions of antibodies to C-terminal fragment of the receptor of angiotensin II - C12, C30, C200 in the dose of 9 ml/kg/day
Groups of animalsFunctional
Naya sample
GARDEN, mm HgDBP, mm Hg's vascular reactions when conducting EDVD with AH and AND with NP, usledQED, the river. units
Control (daily intragastric administration of distilled water and 9 ml/kg/day)Source159,2±5,4to 124.2±4,71,2±0,1
OHto 96.9±6,752,0±3,03071,2±501,1
NP113,8±6,155±2,43617,2±560,1
Treated with L-NAME (12.5 mg/kg)Source204,8±10*164,2±5,9*3,5±0,5*
OH111,3±7,464,7±4,3*3700,2±536,9
NP118,2±9,961,4+4,411922,8±1838,9*
L-NAME (12.5 mg/kg)+mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial NOS man - C12, C30, C200 (9 ml/kg/day)Source230,1±8,8*175,1±6,4*1,8±0,2**
OH116,4±4,0*73,5±3,5*5826,0±801,2**
NP108,1±4,660±3,69628,5±970,1*
L-NAME (12.5 mg/kg)+mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial NOS man - C12, C30, C200 (9 ml/kg/day)+mixture of solutions of homeopathic dilutions of antibodies to C-terminal fragment of the receptor of angiotensin II-C12, C30, C200 (9 ml/kg/day)Source213,6±4,6*166,8±,7* 1,4±0,1**
OH116,9±5,5*73,3±3,4*3295,3±201,4
NP122,3±4,670,5±4,5*4546,2±299,4**
Note: * - p<0,05 in comparison with the control group; ** p<0,05 in comparison with the group of L-NAME. GARDEN - systolic blood pressure, DBP - diastolic blood pressure, S is the area above the curve recovery of blood pressure when conducting pharmacological tests, CED - factor for endothelial dysfunction.

In the group of animals, where the infusion of L-Name at a dose of 12.5 mg/kg for 28 days were intragastrically administered a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person, at a dose of 9 ml/kg - C12, C30, C200 in complex with a mixture of solutions of homeopathic dilutions of antibodies to C-terminal fragment of the receptor of angiotensin II - C12, C30, C200 QED amounted to 1.4±0,1), which is significantly lower than in the group with the modeling of pathology and in the group with mono correction with a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to indotel the social-synthase nitric oxide person, at a dose of 9 ml/kg - C12, C30, C200.

Thus, the obtained results allow to state correction L-Name-induced endothelial the infusion of L-Name at a dose of 12.5 mg/kg for 28 days with a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person, at a dose of 9 ml/kg - C12, C30, C200 in complex with a mixture of solutions of homeopathic dilutions of antibodies to C-terminal fragment of the receptor of angiotensin II - C12, C30, C200, after intragastric administration at a dose of 9 ml/kg each of them, reducing QED to the level of those in the control group of animals - 1,2±0,1 usled

Method of correction of endothelial dysfunction solution of homeopathic dilutions of antibodies to endothelial synthase nitric oxide person in the complex with a solution of homeopathic dilutions of antibodies to C-terminal fragment of the angiotensin II receptor, characterized by the fact that in the experiment the rats male Wistar within 28 days, on the background of intraperitoneal administration of L-Name at a dose of 12.5 mg/kg, daily, 2 times daily 4.5 ml/kg (9 ml/kg/day), intragastrically injected a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase nitric oxide person - C12, C30, C200, at a dose of 9 ml/kg in combination with a mixture of solutions of homeopathic dilutions of antibodies to the C-terminal fragment of the receptor of angiotensin II - C12, C30, C200 (2 times daily 4.5 ml/kg (9 ml/kg/day), intragastrically.



 

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