Tonus of the vascular wall

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Description of the pharmacological group

Medicines affecting the tone of the vascular wall

Smooth muscles generally and smooth muscles of vessels in particular in their anatomist- functional properties differ significantly from the transversostriated musculature.

Smooth-muscle cells have spindle-shaped form and are circular (from Lat. circularis - circular, in the circle) located in the wall of vessel. The smooth-muscle cells of vessels, just as the cell of myocardium, are connected together by inserting disks - Nexus (from Lat. nexus - connection), through which electric pulses are transferred from the cell to the cell.

Just as in the transversostriated musculature, the reduction of smooth muscles occurs because of the slip relative to each other of the threads of actin and myosin. However, in contrast to the cells of skeletal musculature and myocardium in the smooth-muscle cells the threads of actin and myosin are not united into the regularly repetitive sarcomeres with the strictly defined structure. Therefore smooth-muscle cells with their study under the microscope lose characteristic for the skeletal musculature and the myocardium transverse striation. Hence and the name of this group of cells - smooth or smooth-muscle cells. In the smooth-muscle cells of the thread of actin it is much longer than in the transversostriated muscle, and many of them are fastened directly to the internal surface of cellular membrane. It is possible that precisely because of the absence of the organized sarcomeres and the large length of the threads of actin, smooth-muscle cells develop stress in the large scale of length, than skeletal or heart muscle. Because of this structure smooth-muscle cells are well adapted to the long run reduction, to guarantee of which in contrast to the transversostriated muscle a small quantity of energy is required - smooth muscle per unit of cross-sectional area with the stress expends 100 - 500 times of less energy than skeletal and heart muscles.

The cells of smooth musculature, just as the cell of the transversostriated and heart musculature, possess the potential of rest, but its value below varies in the limits from -40 to -65 mV. The value of the potential of the rest of smooth-muscle cells in essence determines the transmembrane ion ion currents K⁺. Large role in the forming of the potential of rest belongs to the so-called transmembrane K⁺- channel of rectified of that directed inside the potassium current (this term means that the ions K⁺ with the larger ease penetrate through this channel the cell, than they leave through it into the intercellular space).

The action potential of smooth-muscle cells in contrast to the cells of the transversostriated and heart muscles is generated not by the ions of Na⁺, but by the ions Ca²⁺, which penetrate the cell through the slow voltage-sensitive calcium channels; therefore a change in the charge of the membrane occurs more slowly, but very action potential is called “slowly increasing”. The ion current Ca²⁺, which causes depolarization (phase of 0 action potential), is directed inside the cell.

The phase of the repolarization of action potential is achieved predominantly due to the output from the cell of the ions K⁺ both through the potassium channels of slow rectification and through the potassium channels activated by the ions Ca²⁺.

The reduction of smooth-muscle cells generally and the smooth-muscle cells of vessels in particular can be caused not only by the depolarization of their cellular membrane, caused by the entrance of the ions Ca²⁺ inside the cell, but also due to the so-called pharmacomechanical withvoltage, or effect, i.e., due to not the electrical, but chemical factors, which cause the reduction of smooth muscle or, in other words, without the generation of action potential. By an example of pharmacomechanical withvoltage can serve the reduction of the smooth-muscle cells of vessels in response to the stimulation of α₁- postsynaptic adrenoreceptors as noradrenaline.

In this case after interaction of noradrenaline with the α₁- adrenoreceptors the excitation of the signal G_q- protein, located on the internal surface of the membrane of the smooth-muscle cell of the vessel, which activates intracellular ferment phosphorylase C, occurs, and it in turn initiates an increase in the content in the smooth-muscle cell of second messengers diazilglycerol and inositoltriphosphate. Further process can be developed by the following way.

Diazilglycerol activates in the cell the ferment diazilglycerolic protein kinase C, which causes the phosphorylation of the slow hemocontrolled transmembrane current of the Ca²⁺- channel, through which the ions Ca²⁺ enter the cell, where they the drive chain of the sequential biochemical processes, which initiate the reduction of cell.

Inositol -1,4,5-triphosphate reaches the sarcoplasmic reticulum, where “is opened” the specialized channel, through which the ions Ca²⁺, deposited in the sarcoplasmic reticulum, leave into the cytoplasm, where they interact with the intracellular protein by calmodulin. The formed complex “calcium- calmodulin” activates calcium -calmodulin dependent protein kinase G, which converts transmembrane slow hemosensibility calcium channels to the open state, and the ions Ca²⁺ enter inside the cell.

Under the normal physiological conditions ion concentration Ca²⁺ in the cytoplasm of cell varies in limits of 10-6- of 10-7 mole/l. When ion concentration Ca²⁺ in the smooth-muscle cells descends below 10 ⁸ mole/l, they begin to weaken. Usually this state is developed as a result the hyper-polarization (increase in the negative charge) of cellular membrane. Smooth-muscle cells differ from the cells of the transversostriated or heart musculature, since the process of the removal of the ions Ca²⁺ and/or absorption by its sarcoplasmic reticulum occurs sufficiently slowly. The removal of the ions Ca²⁺ entails the dephosphorylation of the heads of myosin and they lose the ability to interact with the threads of actin.

The hyper-polarization of cellular membrane is reached via the blockade of the transmembrane potential dependent K⁺- channels or by pharmacomechanical interaction, for example by the excitation of beta₂- adrenoreceptors. The excitation of the beta₂- adrenoreceptors, located on the membranes of the smooth-muscle cells of vessels, entails the activation of the signal G_S- proteins, which in turn activate ferment adenylate cyclase.

The latter contributes to an increase in the content inside the cells of second Messenger cAMP. However, smooth-muscle cells in contrast to the cells of the transversostriated and heart musculature, where cAMP activates not cAMP- dependent ferment protein kinase A, but specialized protein kinase, which causes the dephosphorylation of the heads of myosin, as a result they lose the ability to interact with the threads of actin. In other words, if in the cells of the transversostriated and heart musculature an increase in the content cAMP in the cells is accompanied by an increase in their contracting ability, then in the cells of smooth musculature, including the smooth-muscle cells of vessels, an increase in the content cAMP entails their weakening.

There are also data about that which in the smooth-muscle cells cAMP contributes to the absorption of calcium ions Ca²⁺ by sarcoplasmic reticulum, which also makes its contribution to the weakening of cells.

Tonus of the vascular wall are used to treat diseases of the vessels of the brain and peripheral vessels