Research Department of Experimental Pharmacology and Physiology

 
Mikhail Pliss
Head of Department

The Research Department of Experimental Pharmacology and Physiology upon the inception of Almazov National Medical Research Centre.

Major research areas

The research focuses on the physiology and pharmacology of the central circulatory regulation. The results of many years’ research led to the concept that high blood pressure can be successfully lowered with centrally acting drugs only if the drug compounds have the ability to influence the tonic activity of sympathetic vasomotor neurons. For the first time, mechanisms have been identified that provide an adaptive increase in blood pressure during aversive emotiogenic influences. The research team of the Department has proved that the mechanism of blood pressure increase induced by negative and positive emotions is due to the involvement of different types of central regulatory mechanisms.

A large part of research is devoted to the neurochemical organization of the central regulatory mechanisms. It was proved that the functional activity of imidazoline systems is higher in animal models of arterial hypertension than in normotensive animals. Studies have revealed that imidazoline systems are also involved in the functioning of central pathway of baroreceptor reflex. Imidazoline receptors are involved not only in the activation of baroreceptor reflex arc on the bulbar level, but also in suprabulbar modulation processes of the reflex mediated by emotional stress.

In addition, an intensive research of the nervous regulation of trophic processes in the heart muscle and dependency of tissue disorders on changes in the functions of both central and peripheral nervous system was conducted. It has been shown that catecholamine influences not only the structural changes in the myocardium, but also causes morphological disorders of the vascular smooth muscle.

The experiments of the Department attempted to influence the development of target organ damage processes during the early postnatal period in the spontaneously hypertensive rats as an adequate model of human hypertension. It has been proved that reduction of the sympathetic activity in the prenatal and early postnatal periods inhibits the development of hypertension and prevents vascular remodeling of resistance vessels in an animal model.

Studies of recent years were aimed at exploring the role of arterial baroreceptor reflex in the long-term control of blood pressure. The researchers of the Department have demonstrated that arterial baroreceptor reflex is involved in the long-term regulation of blood pressure and inhibits its long-term increase in response to a stimulus.

Major achievements and results

The researchers of the Department have proved that the mechanism of increase in blood pressure induced by both negative and positive emotions is mediated by the activation of different types of central regulatory mechanisms. The research cycle in this area was approved as a scientific discovery “Baroreflex regulation of blood pressure in mammals under the influence of emotional stress” (No. 116, 1997).

The research team has demonstrated that arterial baroreceptor reflex is involved in the long-term regulation of blood pressure and inhibits its long-term increase in response to a stimulus. The International Academy of Authors of Scientific Discoveries and Inventions recognized these studies by issuing the certificate of scientific discovery “Blood pressure regulation in humans and animals under the influence of baroreceptor reflex” (No. A-503, 06 May 2010).

Ongoing research and prospects for development

Many various factors are currently known to be associated either directly or indirectly with the development of remodeling of myocardium and vascular smooth muscles, but there is still no clear answer about the remodeling mechanisms. The analysis of the circumstances underlying these processes suggests that a common factor is the increased activity of the sympathetic nervous system. Hence, one of the problems faced by researchers is to clarify the role of the sympathetic nervous system in the functioning of these mechanisms controlling the growth and development of excitable tissues (cardiomyocytes, vascular smooth muscles) and remodeling of cardiovascular system.

The second research problem is to identify factors that enhance the activity of the sympathetic nervous system in simulated cardiovascular disease. The first step in this area will be an analysis of blood pressure changes and activity of vasomotor neurons in cardiovascular mechanoreceptor denervation in long-term chronic experiments using telemetry monitoring of the major hemodynamic parameters.

The third problem for the Department in the near future will be the study of afferent baroreceptor role in simulated arterial hypertension.

Participation in Government Projects

The researchers of the Department were involved in the project of the RAS Presidium “Fundamental Science to Medicine” on the research topic “Creating of macromolecular systems with antioxidant properties to protect cells from ischemia/reperfusion injury”, in the Federal Target Programme “National Technological Base” for 2007–2011, approved by the Government of the Russian Federation on January 29, 2007, No. 54.

Currently, the researchers are working under grant No. 12-04-00941-a of the Russian Foundation for Basic Research “Cardiotonics and weak magnetic proliferation modulation of resident progenitor cells and skeletal muscle of rat myocardium in primary culture (2012–2014)”. In addition, researchers are involved in the Project of the Russian Ministry of Health “Study of cardiovascular autonomic blood circulation and adaptation mechanisms to physical stress”.

Major publications

Tsyrlin V. A., Bravkov M. F. Effects of alpha-adrenoceptor stimulating drugs on baroreceptor reflex in conscious cats // Eur. J. Pharmacol. – 1980. – Vol. 67. – P. 75-83.

Tsyrlin V. A., Bravkov M. F. Bershadsky B. G. Possible mechanisms underlying the pressure responses evoked in conscious cats by emotional stress // Pflugers Arch. – 1983. – B. 398. – S. 81-87.

Tsyrlin V. A., Pliss M. G., Patkina N. A., Bershadsky B. G., Eremeev V. S. Baroreceptor reflex inhibition as a mechanism for raising blood pressure under negative emotions / In: Systems Research in Physiology // Amsterdam: Gordon and Breach Science Publishers. – 1989. – Vol. 3. – P. 329-341.

Penniyainen V. A., Lopatina E. V., Krylov B. V. The effect of sodium pump inhibitors on sensory ganglion neurite growth // Neurosciences and Behavioral Physiology. – 2009. – Vol. 39. – № 3. – P. 301-305.