[Pulmonary artery denervation in pulmonary hypertension: physiological and clinical aspects]. / Denervatsiia legochnoi arterii pri legochnoi gipertenzii: fiziologicheskie i klinicheskie aspekty.

This article is a review of the findings of experimental and clinical studies of a new method of treatment of pulmonary hypertension - pulmonary artery denervation with the help of radiofrequency ablation, cryodenervation and ultrasonic impact. Pulmonary artery denervation results in decreased neurogenic tonic sympathetic and, probably, increased parasympathetic effects on pulmonary vessels. On models of experimental monocrotaline-induced pulmonary hypertension in various-species animals, it was determined that pulmonary artery denervation is followed by decreased activity of local pulmonary renin-angiotensin system, slowed processes of remodeling of pulmonary vessels, hypertrophy and fibrosis of the right ventricle, with inhibition of progression of pulmonary hypertension by means of suppression of extracellular signal-regulated kinase 1/2 (ERK 1/2) which regulates differentiation, proliferation and migration of smooth muscle cells. However, the problem of the pattern of pulmonary microcirculation changes (pre- and postcapillary resistance, capillary filtration coefficient) after pulmonary artery denervation warrants further study. The findings of clinical studies in patients with pulmonary hypertension suggest that pulmonary artery denervation inducing a decrease of pressure therein, as well as pulmonary vessel resistance did not lead to normalization of pulmonary haemodynamics.The mentioned impact partially removes the neurogenic component of multicircuit and multifactorial regulation of pulmonary circulation. Therefore, along with pulmonary artery denervation, further search for pharmacological agents selectively influencing pulmonary vessels remains a problem of current importance.

[MECHANISMS OF GASTRODUODENAL DYSMOTILITY UNDER STRESS].

Psychogenic stress in rabbits caused dysmotility of the gastroduodenal zone: inhibition of contractile activity (CA) in antral and pyloric parts of the stomach simultaneously with the increase of CA in proximal and distal parts of duodenum. Stress induced inhibition of the gastric contractile activity is substantially "non-adrenergic non-cholinergic" and only in the initial phase of the reaction it appears to be "α-adrenergic". The strengthening of CA in the proximal duodenum resulted from the direct exciting action of endocrine stress factor on the smooth muscle of the gut. The strengthening of the CA in the distal duodenum is a result of the endocrine action of catecholamines on stimulating ß-adrenergic receptors of enteric cho linergic neurons. Stress induced dyscoordination of the gastroduodenal motility can cause duodenogastric reflux and as a consequence, erosive damage of the gastric mucosa.

Changes in contractile activity of rabbit colon under stress conditions and during post-stress period before and after blockade of muscarinic and nicotinic cholinergic receptors.

Psychogenic stress in rabbits induced by fixation of the animal to a frame was accompanied by an increase in contractile activity of the initial portion of the distal colon, which was abolished by blockade of muscarinic and nicotinic cholinergic receptors. Increased contractile activity of the colon was due to centrogenic stimulation of preganglionic neurons of the parasympathetic nervous system followed by the involvement of the effector cholinergic neurons of the enteric nervous system into excitation.

[Symptoms of circadian desynchronization in patients with multiple sclerosis].

Circadian rhythm of sleep-wakefulness and evacuation function of intestines, symptoms of neuropsychic adaptation were investigated in 36 patients, aged 21-53 years, with multiple sclerosis (MS). Frequencies of circadian rhythm disturbances of brain activity (insomnia in 66% of patients) and circadian rhythm disturbances of intestine evacuation (constipation in 72% of patients) were revealed. Insomnia and irritability in MS patients with bradyenteria occur 1.5 times more frequent than in patients with normal regulative activity of the bowels. The risk of anxiety and depression in MS patients with bradyenteria was 2-3 times higher than in patients with euenteria. The suitability of normalization of circadian desynchronization of MS patients by the restoration of optimal acrophases of circadian rhythms of the brain and bowels is established.

[Changes of contractile activity of the colon under psychogenic stress before and after blockade of M- and N-cholinergic and beta-adrenoceptors].

In experiments on conscious rabbits, myoelectric activity (contractile activity index) was recorded in 2 sites of proximal and in 2 sites of distal part of the colon under psychogenic stress induced by firm fastening of the animal to a frame in supine position. Stressor impact caused decrease of the contractile activity in proximal and distal parts of the colon, due to "alpha-adrenergic" (in initial stage of stress reaction) and "nonadrenergic noncholinergic" inhibition. Stress-induced increase of the contractile activity of the colon was limited to the initial segment of its distal part, and was due to centrogenic stimulation of the preganglionic neurons of the parasympathetic nervous system and effector cholinergic neurons of the enteric nervous system.

Changes in contractile activity of the duodenum, jejunum, and ileum under conditions of psychogenic stress in rabbits.

Psychogenic stress in rabbits caused by fixation of the animal to a frame was accompanied by an increase in duodenal contractile activity. In the jejunum, initial inhibition of motor activity gave way to activation more pronounced in the proximal part. In both parts of the ileum, inhibition of contractile activity was noted. A proximodistal gradient of the excitatory and inhibitory effects on the motility of the small intestine was demonstrated.

[Interrelation of hemodynamic changes in systemic and pulmonary circulation under experimental myocardial ischemia in cats].

Myocardial ischemia caused inhibition of myocardial contractility, increased pressure in the left atrium, reduced cardiac output and reduced systemic blood pressure. The decrease in cardiac output is due to a combination of the myocardial contractility reduction and that of the outflow of blood from the pulmonary vascular bed. Hemodynamic changes in the arterial part of the systemic circulation are accompanied by shifts in its venous part: reduced blood flow in the anterior and posterior caval veins and a decrease in venous return. The determining factor for reducing the flow of venous blood to the heart during myocardial ischemia is a decrease in cardiac output. Myocardial ischemia of the left ventricle is accompanied by a decrease in pressure and blood flow in the pulmonary artery. The data obtained suggest that the degree of reduction of these indicators of pulmonary hemodynamics depends on the elevated pressure in the left atrium resulting from reduction of the left ventricle contractility. The degree of hemodynamic disorders in systemic and pulmonary circulation in myocardial ischemia depends not only on the size of the zone of myocardial ischemia of the left ventricle, but also on the duration of cessation of its blood supply. We suggest that the time factor is a decisive one with respect to severity of hemodynamic disorders occurring only at a certain, critical, size of the zone of myocardial ischemia.

[Mechanism of inhibition of the contractile activity in the jejunum and ileum under psychogenic stress in rabbits].

In chronic experiments on rabbits, myoelectric activity (contractile activity index) in proximal and distal part of the jejunum and proximal part of the ileum was studied under psychogenic stress caused by rigid fastening of the rabbit to table in supine position. Inhibition of contractile activity in the proximal and distal parts of thejejunum in the 1st phase of the stressor response manifested on the background of blockade of presynaptic alpha 2-adrenoceptor with yohimbin, nonselective blockade of alpha-adrenoceptor with dihydroergotoxin, or blockade of beta 1/beta 2-adrenoceptor with propranolol. Conclusion is made that the stressor inhibition of contractile activity in the proximal and distal parts of the jejunum was not "adrenergic cholinergic" or "adrenergic" in origin. The contractile activity inhibition of the jejunum was actualized with the contribution of "nonadrenergic noncholinergic" inhibitory mechanism and mediated via nonadrenergic inhibitory neurons of the enteric nervous system. Depression of the contractile activity in the proximal part of ileum being preserved after blockade of presynaptic "alpha 2-adrenoceptor" or blockade of beta 1/beta 2-adrenoceptor, was not "adrenergic cholinergic" or "beta-adrenergic". Nonselective blockade of alpha-adrenoceptor resulted in diminished stressor inhibition of the contractile activity in the proximal part of ileum. The data obtained suggest that the stressor inhibition of the contractile activity in the proximal part of ileum was caused by "nonadrenergic noncholinergic" inhibitory mechanism with participation of the "alpha-adrenergic" inhibition. The "nonadrenergic noncholinergic" inhibition of the contractile activity in the jejunum and ileum might result from activation of enteric inhibitory neurons with a stressor factor of hormonal nature.

[Mechanism of strengthening of the contractile activity in the duodenum and in the jejunum in psychogenic stress in rabbits].

In experiments on unanaesthetized rabbits myoelectric activity (contractile activity index) of proximal (postpyloric) and distal sites of duodenum, and proximal part of jejunum was studied under stress induced by fastening a rabbit to a table in supine position. In both sites of duodenum, the stress impact induced a short-time decrease of contractile activity which was followed by its increase that exceeded the initial level. In the proximal part ofjejunum, the increase of contractile activity took place only during the second part of stress response. The strengthening of the contractile activity of the proximal part of duodenum was preserved after muscarinic or nicotinic cholinoceptor blockage, and after beta-receptor blockage. It was concluded that the contractile response of the proximal part of duodenum did not result from the contribution of central or local neurogenic mechanism, including excitatory cholinergic one, but was humoral in origin. The strengthening of the contractile activity of the distal part of duodenum and proximal part ofjejunum was abolished by muscarinic cholinoceptor and beta-receptor blockage, and resulted from the action of circulating catecholamines on the excitatory beta-adrenoceptor, localized on the cholinergic neurones of the enteric nervous system.

[On the mechanism of gastroduodenal motility inhibition under psychogenic stress in rabbits].

In experiments on unanaesthetized rabbits, myoelectric activity (contractile activity index) in antral and pyloric parts of the stomach and in two sites of proximal duodenum was studied under stress induced by fastening rabbit to a table in supine position. The stressor impact induced inhibition of contractile activity in antrum and pylorus. The duodenal contractile activity after initial complete suppression overshot its initial level. Blockade of beta1/beta2-adrenoceptor with propranolol and blockade of alpha2-adrenoceptor with yohimbine did not influence qualitatively the pattern of the stressor responses of antrum and pylorus, and of the postpyloric part of duodenum. In conditions of unselective blockade of alpha-adrenoceptor with dihydroergotoxin there was no initial complete inhibition of duodenal contractile activity, and its strengthening was more expressed than in the control experiments. The received data indicate that the stressor inhibition of antral and pyloric contractile activity possibly results from activation of non-adrenergic inhibitory neurons of the enteric nervous system. The initial short-term suppression of duodenal motility resulted from its "adrenergic" inhibition which can also be a factor limiting the manifestation of stimulating effect of the humoral agent on the duodenal motility. In the period after release of the animal, index of antral and pyloric contractile activity did not significantly differ from its initial level; after beta1/beta2-adrenoceptor blockade in antral and after alpha2-adrenoceptor blockade or nonselective alpha-blockade in antral and pyloric parts of the stomach, there was decrease of contractile activity compared with its initial level; after alpha2- or beta1/beta2-adrenoceptor blockade there was no poststressor exceeding of the initial level of the duodenal contractile activity, observed in the control experiments.

[Contractile activity of duodenum, jejunum, and ileum at psychogenic stress in rabbits before and after muscarinic or nicotinic cholinoceptor blockade].

In chronic experiments on rabbits, myoelectric activity (contractile activity index) in distal part of the duodenum, proximal and distal parts of the jejunum and proximal part of the ileum was studied under psychogenic stress caused by rigid fastening rabbit to a table in supine position. In duodenum, the stressor impact rendered stimulating, and in an ileum--inhibitory influence on their motility. In a jejunum the inhibition with the subsequent stimulation was observed, the latter being more expressed in a proximal part of the intestine. The proximo-distal gradient of exitatory and inhibitory influences of the psychogenic stress on contractile activity of the small bowel was revealed: in distal direction, inhibitory influences strengthen and stimulatory ones weaken. The muscarinic receptor blockade abolished increase of the duodenal and jejunal contractile activity obsereved in the control. The nicotinic cholinoceptor blockade abolished increase of the duodenal contractile activity in the 1-st phase of the stressor response and did not exclude an increase of the duodenal contractile activity in the 2-nd phase of the response. Muscarinic or nicotinic blockade did not influence the manifestation of the inhibitory reaction of proximal part of the ileum. In the period after release of the animal, the duodenal and jejunal contractile activity exeeded its initial level. This exeeding did not preserve after muscarinic cholinoceptor blockade but did preserve after nicotinic one in duodenum and proximal jejunum. The received data allow to conclude, that produced by the stress increase of the contractile activity of the distal part of duodenum, proximal and distal parts of jejunum produced by the stress, as well as exceeding the initial contractile activity level in the period after release of an animal, are mediated by cholinergic effector neurones of the enteric nervous system.

[The mechanism of the duodenal motility strengthening under psychogenic stress in rabbits].

In experiments on unanaesthetized rabbits, myoelectric activity (contractile activity index) of two sites of duodenum and of antral and pyloric parts of the stomach was studied under stress induced by fastening a rabbit to a table in supine position. In both sites of duodenum, the stress impact induced a short-time inhibition of contractile activity which was followed by its strengthening that exceeded the initial level. Meanwhile in antrum and pylorus, the whole period of stress impact was characterized by suppression of contractile activity, the latter being more pronounced in the antrum. The strengthening of the duodenal contractile activity was preserved after muscarinic ornicotinic cholinoceptor blockade. It was concluded that the contractile response of duodenum seemed to be of humoral origin.

[Mechanisms of inhibition of the contractile activity in the ileo-caecal zone in rabbits under psychogenic stress].

In experiments on unanaesthetized rabbits, myoelectric activity (contractile activity index) of distal ileum, caecum, and proximal colon in two sites was studied under stress induced by fastening a rabbit to the table in supine position. The stress caused sharp decrease (up to complete disappearance) of the contractile activity in all studied compartments of the ileocaecal intestine with partial or complete restoration after release of the animal. Nonselective blockade of pre- and postsynaptic alpha-adrenoceptor with dihydroergotoxin abolished the initial component of the specified inhibitory response. The latter was caused by "adrenergic inhibition" as a result of action of catecholamines circulating in blood on inhibitory smooth muscle alpha-adrenoceptor. Against the background of muscarinic cholinoceptor blockade, the stressor inhibition of ileocaecal contractile activity observed in control experiments was completely preserved. The periods of supression of ileoceacal contractile activity under stress resistant to blockade of alpha-, beta-adrenoceptor and muscarinic cholinoceptor, are caused by the mechanism of "nonadrenergic noncholinergic inhibition", which is realized at the expence of activation of the enteric inhibitory neurones.

[Mechanisms of serotonin effect on motility of ileocaecal zone in alert rabbits].

I.V. administration of serotonin (2 mg kg(-1)) to alert rabbits changed the ileal, caecal, and colon motility including excitatory and inhibitory components. Initial rise of contractile activity was quickly replaced by its diminishing followed by a longer enhancement of the motility, and then by the final, inhibitory, phase. Under blockade of beta1- and beta2-adrenoreceptors with propranolol inhibition of ileal and caecal contractile activity with serotonin was preserved, the effect of circulating catecholamines on beta-adrenoreceptors of smooth muscle cells seems to be excluded as a cause of the serotonin inhibitory effect. In conditions of blockade of pre- and postsynaptic alpha-adrenoreceptors with phentolamine, there was no significant diminishing of the contractile activity in the ileo-caecal zone below the initial level induced by serotonin in control experiments. Intensification of the ileo-caecal zone contractile activity under the effect of serotonin persisted in conditions of blockade of muscarinic cholinoreceptors and was proceeding with participation of non-cholinergic excitatory mechanism.

[Mechanism of the serotonin effect on motility of the duodenum, ileum, and jejunum in awake rabbits]. / Mekhanizmy vliianiia serotonina na motornuiu aktivnost' dvenadtsatiperstnoi, toshchei i podvzdoshnoi kishki u bodrstvuiushchikh krolikov.

I. v. administration of serotonin to alert rabbits produced a phasic change of contractile activity of duodenum, ileum, and jejunum including excitatory and inhibitory components. It is shown that stimulation of the small bowel motility is caused by serotonin activation of non-cholinergic excitatory mechanism with participation of effector cholinergic neurones. The initial suppression of the motility is caused by participation of nonadrenergic noncholinergic inhibitory mechanism, and the secondary inhibition of contractile activity of a small bowel with serotonin has an adrenergic nature.

[Non-adrenergic mechanisms of inhibition of the contractile activity of the cat small intestine by histamine, bradykinin, and met-enkephalin]. / Neadrenergicheskie mehanizmy tormozheniia sokratitel'noi aktivnosti tonkoi kishki koshek gistaminom, bradikininom i met-énkefalinom.

I. a. histamine and bradykinin caused both an activation and an inhibition of jejunal contractile activity. The inhibitory effect was preserved after blockade of muscarinic cholinoreceptors, alpha- and beta-adrenoceptors, and abolished with the nicotinic cholinoceptor blockade. Metenkephalin inhibited the jejunal contractile activity after first activating it. The inhibitory effect of the peptide was preserved after blockade of alpha- and beta-adrenoceptors as well as the nicotinic cholinoceptors. The data obtained suggest that the non-adrenergic inhibitory effect of metenkephalin on intestinal contractions was the result of its depressing action on motor cholinergic neurons, whereas the inhibition of intestinal contractile activity with histamine and bradykinin resulted from their activating action on cholinergic interneurons which activate non-adrenergic inhibitory neurons through nicotinic cholinoceptors.

[Stress-induced inhibition of the ileal, caecal, and colonic contractile activity in rabbits]. / Stressornoe tormozhenie sokratitel'noi aktivnosti podvzdoshnoi, slepoi i tolstoi kishki u krolikov.

In alert rabbits, immobilisation stress decreased the spike burst rate and amplitude in ileum, caecum, and colon for 20 min. Following beta-adrenoceptor blockade, the contractile activity suppression was aggravated. The stress seems to lead to suppression of the ileal, caecal, and colonic contractile activity for up to 40 min which is unrelated to adrenergic inhibition of the smooth muscle activity mediated by beta-adrenoceptors.