Study of pharmacological agents affecting cardiovascular system

• The study of hypotensive action of PA includes:
  • the assessment of PA influence on angiotension-converting enzyme (ACE) activity.
  • the study of antihypertensive influence of PA is carried out in spontaneously hypertensive rats (SHR) using the following models:
    • mezatonum model;
    • izadrinum model.

• The study of PA efficiency in treating of coronary blood circulation disorders is performed in the following model:
  • the model of an experimental myocardial infarction.
• The study of PA activity in pulmonary crotalin-induced hypertensia model;
• The study of PA specific effect on blood vessels of chicken embryo chorioallantoic membrane includes an assessment of three mechanisms of PA action:
  • noradrenergic mechanism;
  • renin-angiotenzin mechanism,
  • endotelial mechanism (activation of endotelial NO-synthase).

• Assessment of PA activity in diabetes model accompanied with an assessment of a capillary protective action is performed using the following models:
  • the model of an acute damage of the vascular bed by hydrogen peroxide;
  • the model of a prolonged diabetes complicated by micro- and (or) macroangiopathy;

• Assessment of PA activity in the model of chronic heart failure (CHF) of a total type;
• Assessment of PA activity in the model of CHF induced by sterile silicone oil (1 ml per 100 g body weight) administrated into both pleural cavities;
• Assessment of cardioprotective effect of PA (cardiotonic and antiarrhythmic) in the isolated heart model by Langendorff Method;
• Evaluation of the activity PA model dosed supravalvular stenosis in mini-pigs or rabbits;
• Antiarrhythmic activity in the study of PA aconite, adrenalin, barium chloride or other models;
• A study of antiarrhythmic activity of PA on models of ventricular arrhythmias;
• A study of antiarrhythmic activity of PA on models of reperfusion arrhythmias;
• Study anti fibrillar activity of PA on mini-pigs, rats;
• Assessment of hypolipidemic and antiatherogenic effects in the model of dislipoproteinemia.

The efficiency of test substances is estimated by the number of animals survived, ECG parameters and the blood pressure value, the biochemical indicators of peripheral blood, CSF and other tissues based on histology, histochemistry and immunohistochemistry analyses.

The procedure of a blood pressure measurement in spontaneously hypertensive rats

The estimated parameters are the follows:

• Total protein,
• Albumin,
• Total lipid level,
• Total cholesterol,
• α-cholesterol,
• Triglycerides,,
• Lipoproteins,
• Creatinine,
• Creatine kinase,
• MV and VV-fractions of creatine kinase,
• Lactate dehydrogenase,
• ALT and AST,
• Lipid peroxidation level, and others.

Histological, histochemical and immunohistochemical studies include:

1. histological assessment of the presence of ischemic tissues and necrotic areas and morphometric analysis of the affected areas;
2. an assessment of morphological parameters of elastic and muscle-elastic type blood vessels and vessels of microvasculature in tissues: heart, lungs, pancreas, mesenteric tissue, brain and eye;
3. histochemical assessment of plasma extravasation in the ischemic tissue;
4. immunohistological assessment of the following parameters:

• the level of an endothelial NO-synthase expression;
• the quantity of angiogenesis marker CD31 (PECAM-1);
• the quantity of proliferation marker Ki67;
• the quantity of proapoptotic marker p53;
• the quantity of antiapoptotic protein Mcl-1.