RU2306953C1 - Method for correction of endothelial dysfunction with solvent mixture of homeopathic dilutions of polyclonal rabbit antibodies to human endothelial nitrogen oxide synthase c12, c30, c200 - Google Patents

Abstract

FIELD: medicine, in correction of endothelial dysfunction.

SUBSTANCE: endothelial dysfunction is modeled in white rats by intraperitoneal administering of endothelial N-nitro-L-arginin methyl ester syntase in dose of 25 mg/kg for 7 days. Further correction is carried out by administering of polyclonal rabbit antibodies to human endothelial nitrogen oxide synthase for C12, C30, C200 for 7 days.

EFFECT: effective correction of endothelial dysfunction.

1 ex, 2 tbl

Description

The invention relates to medicine, in particular to experimental cardiopharmacology.

Closest to the claimed solution is a method for the correction of endothelial dysfunction with statins related to lipid-lowering drugs, described by Rikitake Y, Liao J.K. in Rho GTPases, statins, and nitric oxide, Circ. Res., 2005, No. 9, V. 97 (12), P.1232-1235, which consists in the use of statins for the correction of endothelial dysfunction.

The main disadvantage of this method is that the correction of endothelial dysfunction is associated with an increase in the activity of endothelial nitric oxide synthase (eNOS) and is cholesterol-independent, "pleiotropic", that is, an additional mechanism of action of this group of drugs. In addition, the main component of the correction of endothelial dysfunction with statins is an increase in the bioavailability of nitric oxide associated with the hypolipidemic effects of statins.

While the main mechanism of action of a mixture of solutions of homeopathic dilution of polyclonal rabbit antibodies to endothelial synthase of nitric oxide - C12, C30, C200 is an increase in the number of eNOS, leading to an increase in the content of nitric oxide in the main vascular bed and correction of endothelial dysfunction. Therefore, the results of the correction of endothelial dysfunction associated with an insufficient amount of endothelial NO synthase using statins are unsatisfactory.

The technical result of the invention is a method for correcting endothelial dysfunction, including the use of a mixture of solutions of homeopathic dilution of polyclonal rabbit antibodies to endothelial synthase of nitric oxide - C 12, C30, C200, leading to an increase in the number of eNOS. The technical result is achieved by the fact that, against the background of modeling endothelial dysfunction in the experiment, an intraperitoneal administration to the laboratory animal for 7 days of the NO synthesis blocker of L-nitro-arginine methyl ether (L-NAME) at a dose of 25 mg / kg is carried out by introducing a mixture of solutions homeopathic dilution of polyclonal rabbit antibodies to endothelial synthase of human nitric oxide - C12, C30, C200 by adding to drinking bowls in quantities accepted in homeopathy, with free access to drinking, replacing water in drinking bowls production 1 Referring once daily drunk in a quantitative view of the liquid (20 ± 3 ml on average per animal).

The method is carried out as follows.

The experiments were carried out on white rats male Wistar line weighing 250-300 g. N-nitro-L-arginine methyl ether (L-NAME) was administered intraperitoneally at a dose of 25 mg / kg / day. On the 7th day from the start of the experiment, a catheter is inserted into the left carotid artery under anesthesia (etaminal sodium 50 mg / kg) to record blood pressure (BP), bolus administration of pharmacological agents is carried out in the right femoral vein. Hemodynamic parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) are measured continuously using the sensor and the Bioshell computer program. Functional tests: endothelium dependent vasodilation (ESV) - intravenous administration of acetylcholine (AH) at a dose of 40 μg / kg, endothelium independent vasodilation (ENZV) - intravenous administration of sodium nitropruside (NP) at a dose of 30 μg / kg.

When statistical data processing was calculated, the average value, the standard deviation. Differences were considered significant at p <0.05.

EXAMPLE OF SPECIFIC IMPLEMENTATION.

A bolus intravenous administration of AH for 3-5 seconds led to a sharp drop in blood pressure, reaching a peak in intact animals for systolic pressure (SBP) of 84.3 ± 4.4, for diastolic pressure (DBP) - 38.7 ± 2.8 and for average arterial pressure (SRAD) 53.9 = 1 = 2.7 mm Hg, with a sharp bradycardia developing up to 130-150 beats per minute during the first 2-3 seconds. Recovery of blood pressure occurred on average for 42.2 ± 0.8 seconds after normalization of the heart rhythm. ENZV was also characterized by a decrease in SBP to 83.0 ± 3.7, DBP to 42.1 ± 4.4 and SRAD to 55.7 ± 3.5 mm Hg. followed by complete recovery on average within 45.1 ± 1.0 sec. Blockade of NO synthase by means of prolonged, daily, intraperitoneal administration of L-NAME (N-nitro-L-arginine methyl ester at a dose of 25 mg / kg) for 7 days caused arterial hypertension (SBP - 190.3 ± 6.7 , DBP - 145.0 ± 3.9, SAD - 160.1 ± 4.6 mm Hg) and led to a smaller decrease in blood pressure after administration of AH (SBP to 110.6 ± 5.2, DBP to 82 , 8 ± 6.6, SAD up to 92.1 ± 6.1 mm Hg) and NP (SAD up to 88.7 ± 4.7, DBP up to 50.8 ± 4.2 and SAS up to 63.4 ± 4.1 mmHg) compared with intact animals.

The simultaneous introduction of L-NAME and a mixture of solutions of homeopathic dilution of polyclonal rabbit antibodies to endothelial synthase of nitric oxide - C12, C30, C200 (BD Transduction Labs, USA) by adding to drinkers with free access to drinking did not lead to a decrease in the initial BP values (SBP - 184.3 ± 7.0, DBP - 136.7 ± 6.5 mm Hg). (table 1.).

Table 1 Dynamics of blood pressure and heart rate in modeling nitric oxide deficiency and correction of endothelial dysfunction with a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial nitric oxide synthase - C12, C30, C200. Groups of animals Functional Tests GARDEN, mmHg DBP, mmHg Heart rate, beats in min Intact Source 137.7 ± 3.7 101.9 ± 4.3 420.0 ± 9.0 EZV with AH 84.3 ± 4.5 38.7 ± 2.8 416.0 ± 14.0 ENZV with NP 83.0 ± 3.7 42.1 ± 4.4 415.0 ± 10.0 Receiving L-NAME (25 mg / kg) Source 190.3 ± 6.7 * 145.0 ± 3.9 * 428.0 ± 11 EZV with AH 110.6 ± 5.2 * 82.8 ± 6.6 * 426.0 ± 14.0 ENZV with NP 88.7 ± 4.7 50.8 ± 4.2 426.0 ± 13.0 L-NAME (25 mg / kg) + a mixture of solutions of homeopathic dilution of polyclonal rabbit antibodies to human endothelial NOS - C12, C30, C200 Source 184.3 ± 7.0 136.7 ± 6.5 417.1 ± 13.1 EZV with AH 91.0 ± 2.1 ** 53.1 ± 4.6 ** 401.0 ± 12.0 ENZV with NP 94.3 ± 4.6 57.8 ± 5.9 427.0 ± 13.7 * - p <0.05 in comparison with the intact group;
** - p <0.05 compared with the L-NAMF group.

The fundamental difference in ESV and ENZV in intact animals and animals with the introduction of an inhibitor of NO synthase L-NAME naturally led us to the necessity of deriving a special indicator characterizing the degree of endothelial dysfunction, which is the ratio of the area of the triangle over the trend in the reaction of restoration of blood pressure in response to the introduction of NP to the area triangle above the trend of the reaction of blood pressure recovery in response to the introduction of AH.

We calculated this ratio for each animal in the intact group and rats after modeling the blockade of NO synthase and obtained a difference of this indicator by a factor of 5 — 1.1 in intact animals and 5.4 in animals treated with L-NAME, respectively.

Thus, for a further assessment of the effect of AH and NP in ESV and ENZV, we used this ratio as an indicator of the correction of endothelial dysfunction. So, in the group where, against the background of the introduction of an inhibitor of N0 synthase L-NAME, a mixture of solutions of homeopathic dilution of polyclip rabbit antibodies to endothelial synthase of human nitric oxide - C12, C30, C200 was introduced (Table 2.).

Thus, the results allow us to state the correction of endothelial against the background of the introduction of L-NAME mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to endothelial synthase of human nitric oxide - C12, C30, C200.

Claims (1)

A method for the correction of endothelial dysfunction, characterized in that in an experiment for white rats, males of the Wistar strain with endothelial dysfunction, against the background of its modeling by intraperitoneal administration of an inhibitor of endothelial synthase N-nitro-L-arginine methyl ester at a dose of 25 mg / kg for 7 days, daily a mixture of solutions of homeopathic dilutions of polyclonal rabbit antibodies to human nitric oxide endothelial synthase — C12, C30, C200 — is added to drinkers for drinking for 7 days.