Hydrogen sulfide does not press

Pyotr Smirnov, "Newspaper.Ru»When one problem has a dozen different solutions, it cannot be excluded that there will be an eleventh.

Perhaps, from such positions, Solomon Snyder from the American Johns Hopkins University and his colleagues in the USA and Canada approached the issue of increasing blood pressure. And for good reason – they managed not just to find a new drug, scientists have created a real springboard for the development of a whole class of drugs.

It is known that useful things do not always have a pleasant taste. Now, as it turns out, the same applies to the smell. Physiologists have irrefutably proved that ordinary hydrogen sulfide, H ₂ S, dilates blood vessels very well. And this mechanism can be used to regulate blood pressure.

The very idea of signaling molecules-gases is not new. Robert Ferchgott, Luis Ignarro and Ferid Murad received the Nobel Prize in 1998 for discovering the role of nitric oxide in the cardiovascular system. And the fact that NO synthesized by endotheliocytes lining the vessels from the inside effectively and, most importantly, rapidly expands small blood vessels is the key to the popularity of nitroglycerin and its derivatives around the world.

A little later, the company NO was CO – carbon monoxide, which, despite its high toxicity, increases the permeability of blood vessels; however, the effect of carbon monoxide is based on its physico-chemical properties, and not on participation in any signaling reaction. Unlike CO, hydrogen sulfide acts not only in critical situations. Snyder and his research team believe that this is a full-fledged regulatory mechanism, in no way inferior to the "Nobel" nitric oxide system.

In all animal organs, "rotten gas" is formed mostly from the amino acid cysteine with the help of the enzyme cystathionine-gammaliase. And in order to study the effect of hydrogen sulfide, scientists genetically blocked – of course, not in humans, but in experimental mice – the production of this enzyme by cells. As a result, there was no hydrogen sulfide in the vessels, although the smell did not disappear from the digestive system – here H2S is synthesized by bacteria, and not by the host organism.

At the same time, the pressure jumped by 18 mmHg in the first two months, and this even in the case when one working copy of the gene was preserved.

The complete shutdown of the gene cost the mutant mice 28 mmHg of "health", and the pressure also increased with age. 28 mm of mercury is no less than 20% of the normal blood pressure level of mice.

All further experiments only confirmed the correctness of Snyder and his colleagues. Chemical analysis confirmed the low level of hydrogen sulfide in the blood, and further physiological experiments irrefutably proved the connection between hydrogen sulfide and blood pressure.

First, the authors of the publication in Science demonstrated that the administration of hydrogen sulfide to mutant mice really reduces blood pressure: with non–toxic doses, they managed to reduce the level by 39 mmHg. art. - an ultra-effective indicator even for the most modern drugs used in clinical practice for this purpose.

According to the researchers, hydrogen sulfide released in endothelial cells diffuses to the smooth muscles of the vessel cell, which changes the current of potassium ions. As a result, the muscles relax, and the vessels expand – and the pressure drops.

Diagram of the structure of the arteries. A) muscle-type artery; B) vessels of the vascular wall; C) muscle strands of the artery wall (arranged in a spiral). 1) outer membrane (adventitia); 2) outer elastic membrane; 3) endothelium; 4) inner elastic membrane; 5) muscle membrane.

Structure of vesselsArteries are vascular tubes lined from the inside with endothelial cells, together with the underlying tissue layer (subendothelium) forming the inner shell.

The middle or muscular membrane of the arteries is separated from the inner by a very thin elastic membrane. The muscle membrane is built of smooth muscle cells. Muscle cells of an almost circular direction lie closer to the inner elastic membrane. Then they follow more and more obliquely, and finally many of them acquire a longitudinal direction. The totality of all muscle elements has the form of strands going in a spiral.

At the same time, the number of spiral layers in children is less than in adults. The degree of inclination of the spiral turns also increases with age. This structure of the muscular membrane ensures the movement of blood in a spiral (swirling blood flow), which contributes to the efficiency of hemodynamics and is energy-efficient.

On top of the muscle membrane lies an external elastic membrane consisting of bundles of elastic fibers. It has no barrier functions and is intimately connected with the adventitia (outer shell), rich in small vessels feeding the artery wall and nerve endings. The outer shell is surrounded by loose connective tissue. The main arteries, together with the companion veins and their accompanying nerve (neurovascular bundle), are usually surrounded by a fascial vagina.

Terminal arteries gradually turn into arterioles, the wall of which loses its division into 3 shells. The endothelium of the arterioles borders on one layer of muscle cells that wrap around the vessel in a spiral. Outside of the muscle cells lies a layer of loose connective tissue consisting of bundles of collagen fibers and adventitial cells. By giving up precapillaries or losing muscle cells, the arteriole passes into a typical capillary. Precapillary or precapillary arteriole is a vascular tube connecting the capillary to the arteriole. Sometimes this part of the microcircular bed is called the precapillary sphincter. Arterioles and precapillaries regulate the filling of capillaries with blood, which is why they are called "regional circulation taps".

Capillaries are the thinnest vessels; they are the main units of peripheral blood flow. After passing through the capillaries, the blood loses oxygen and takes carbon dioxide from the tissues. Along the venules, it rushes into the veins, first into the collecting, and then into the diverting and main ones. The walls of the veins do not have a distinct layering, the boundaries between the shells are weakly expressed. The middle shell is poor in muscle cells. Only the portal vein has a massive muscular sheath, which is why it is called the "arterial vein". In general, the vein wall is thinner, does not differ in elasticity and is easily stretched. The speed of blood flow through the veins and the pressure in them is much lower than in the arteries.

Another fact allowed us to finally draw out the regulation scheme. Going through a variety of medications to reduce blood pressure, scientists found that the introduction of methacholine, an analogue of the mediator acetylcholine, did not lead to a decrease in pressure in mutant mice.

According to scientists, it all starts with the nervous system, which, having decided for some reason that the pressure in the vessels is too high, releases a mediator from the nerve endings. It acts on the vascular endothelium, and endothelial cells form hydrogen sulfide with the help of cystathionine-gammaliase. Since mutant mice do not have this enzyme, metacholine did not help them either.

The fact that in addition to the already known hormonal and nervous regulation systems, another one has been discovered is not so surprising – the body has many duplicate systems. This gives pharmacologists a chance to develop a new class of drugs – in addition to the ten already existing ones.

Currently, several main classes of drugs are recommended for the treatment of hypertension: diuretics (diuretics), alpha- and beta-blockers, calcium antagonists (magnesium supplements), angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and imidazoline receptor agonists. In clinical practice, therapy has to be changed every two to three years, so the need for new drugs is obvious.

However, it is not yet clear how effective such treatment will be. Firstly, it is not known whether hydrogen sulfide deficiency is an important cause of high blood pressure in humans. And secondly, the low solubility of the gas makes it difficult to deliver it to the vessels. But this does not detract from the importance of the work, which demonstrated that not everything is clear in classical physiology either.

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24.10.2008