Effect of Cholecystokinin-8 (CCK-8) on Blood Pressure and Blood Content of Calcitonin-Gene-Related Peptide (CGRP) in Rats with Hypertension Caused by Fructose or Inhibition of Nitric Oxide Synthesis.

We studied the effect of CCK-8 on BP and blood content of CGRP in rats with hypertension caused by fructose or inhibition of NO synthase with L-NAME. The decrease in the CGRP content was found during the development of fructose-induced hypertension, but not L-NAME-caused hypertension. Administration of CCK-8 to fructose-fed animals reduced BP and increased the content of CGRP. In rats with hypertension caused by NO deficit, CCK-8 lowered BP, but did not affect the content of CGRP. These findings suggest that CGRP mediates the hypotensive effect of CCK-8 in fructose-induced hypertension, but not in NO-deficient hypertension.

Effect of Transcutaneous Electrical Stimulation of Nerves on Blood Pressure and Blood Content of Neuropeptide CGRP and Nitric Oxide in Hypertensive Rats with Metabolic Disturbances.

The development of arterial hypertension in male Wistar rats with fructose-induced metabolic syndrome (12.5% of fructose solution as the only drinking source for 10 weeks) along with impaired glucose tolerance and increased serum concentration of triglycerides and LPO products caused a decrease in the content of serum blood calcitonin gene-related peptide (CGRP). Low-frequency transcutaneous electrical nerve stimulation (1 mA, 2 Hz, 10 min daily for 2 weeks) performed in 8 weeks after the beginning of fructose treatment reduced systolic BP and serum concentration of triglycerides and LPO produces and improved glucose tolerance. After stimulation, CGRP content in rats maintained on fructose diet returned to normal values and the content of nitric oxide metabolites increased. We hypothesize that CGRP and nitric oxide are involved in mechanisms mediating the therapeutic effect of low-frequency transcutaneous electrical nerve stimulation on arterial hypertension developing in metabolic syndrome.

[ROLE OF CAPSAICIN-SENSITIVE NERVES IN THE REGULATION OF DEHYDROEPIANDROSTERONE SULFATE BLOOD CONTENT UNDER NORMAL AND FRUCTOSE-INDUCED METABOLIC SYNDROME].

The effects of the stimulation of capsaicin-sensitive nerves (capsaicin, 1 mg/kg, s/c) and their eafferentation (capsaicin, 150 mg/kg, s/c) on the blood content of dehydroepiandrosterone sulfate (DHEAS) was investigated in normal rats and rats with fructose-induced metabolic syndrome (12.5% fructose solution, 10 weeks). An increase in blood of tryglyceride, lipid peroxidation, glucose (fasting and after loading glucose, 2 mg/kg, i/p) was considered as symptoms of metabolic syndrome. It was shown that in normal rats drinking tap water the stimulation of capsaicin-sensitive nerves resulted in the increase of DHEAS content while their deafferentation reduced the concentration of this hormone in the blood. The fructose diet caused the decrease in content of DHEAS, triglyceridemia, lipid peroxidation, impaired tolerance glucose. In rats with the metabolic syndrome the stimulation capsaicin-sensitive nerves prevented the fructose-induced decrease of DHEAS content as well as decreased the symptoms of metabolic syndrome. In fructose fed rats the stimulation-induced effects were prevented by the deafferentation of capsaicin-sensitive nerves. It is suggested that capsaicin-sensitive nerves contribute both to the regulation of blood content of DHEAS under normal and fructose-induced metabolic syndrome.

[The effect of destruction of rat capsaicin-sensitive nerves on blood pressure in rats with metabolic syndrome].

The effect of destruction of capsaicin-sensitive nerve (capsaicin 150 mg/kg, s/c) on blood pre- ssure was investigated in rats with metabolic syndrome induced by fructose (12.5% in drinking water for 10 weeks). The blood plasma concentrations of glucose, triglyceride (TG) and products of lipid perioxidation were defined in these rats. The systolic blood pressure was measured by non-invasive method using the Coda system (Coda, Kent Scientific, USA). The fructose diet caused impaired tolerance glucose, arterial hypertension, increased the contents of TG and products of lipid peroxidation. In capsaicin--pretreated rats (deafferentiation of capsaicin-sensitive nerve) the fructose intake did not evoke impairment tolerance glucose, the increase of systolic blood pressure and the plasma content of triglyceride. The increase of lipid perioxidation in fructose fed rats was not prevented by capsaicin pretreatment. The authors suggest that capsaicin-sensitive nerves contribute to the development of insulin resistance and arterial hypertension in the metabolic syndrome.

[Effects of capsaicin on oxidative modification of blood plasma proteins and arterial blood pressure in fructose-fed rats].

The influence of the activation of capsaicin-sensitive nerves with capsaicin on the oxidative modification of blood plasma proteins and arterial blood pressure was studied in Wistar rats fed with 12.5% fructose in drinking water for 10 weeks. The obtained results indicate that fructose feeding induces an increase in the arterial blood pressure and the content of plasma blood protein carbonyl derivates. At the same time, in hypertensive rats, the stimulation of sensory nerves by capsaicin (1 mg/kg, i.p.) decreases the content of oxidized proteins in the plasma and normalizes the arterial blood pressure. It is suggested that capsaicin-sensitive nerves are involved in the regulation of oxidative destruction of proteins as well as in blood pressure control under metabolic disturbances produced by prolonged fructose feeding.

[Oxidative modification of rat blood proteins after destruction capsaicin-sensitive nerve and change of nitric oxide level].

Content of blood protein carbonyl derivates in rats are determined to assess oxidative modification of protein after destruction of capsaicin-sensitive nerve and change of nitric oxide (NO) level. Deafferentation of these nerves produces increase of the protein carbonyl derivates content. The increase of NO by L-arginine does not affect protein oxidative destruction produced by ablation of capsaicin-sensitive nerve. Selective inhibitor of neuronal synthase NO (n-NOS) 7-nitroindazole (7-NI) results in similar effect. L-NAME increased oxidative destruction of proteins. These results demonstrate that deafferentation of capsaicin-sensitive nerve induces oxidative destruction of proteins. NO has party to mediating oxidative modification of proteins.

[Disturbed microvascular permeability in the eye caused by capsaicin microinjections into the trigeminal caudalis nucleus].

Capsaicin microinjection into the trigeminal caudalis nucleus (the central projection area of trigeminal capsaicin-sensitive nerve) increase extravasation of proteins in rat eye. The effect was inhibited by ruthenium red introduction (a capsaicin receptor antagonist) and by blocking the effector functions of capsaicin-sensitive nerve endings. It is suggested that capsaicin stimulation of central terminations of trigeminal capsaicin-sensitive afferents induce an increase in the microvascular permeability of the eye, which is mediated through the effector function of capsaicin-sensitive nerves.

Role of nitric oxide in the regulation of activity of proteinase inhibitors alpha(1)-antitrypsin and alpha(2)-macroglobulin by capsaicin-sensitive nerves.

Regulation of activity of serine proteinase inhibitor a1-antitrypsin and nonspecific proteinase inhibitor alpha(2)-macroglobulin in the blood by nitric oxide was studied in intact rats and animals with damage to capsaicin-sensitive nerves. Nonselective nitric oxide synthase inhibitor L-NAME produced a dose-dependent increase in alpha(1)-antitrypsin activity in intact animals. Neuronal NO synthase inhibitor 7-nitroindazole increased alpha(2)-macroglobulin activity. Deafferentation with capsaicin was followed by a decrease in alpha(1)-antitrypsin activity. Both inhibitors of nitric oxide synthase increased activity of alpha(1)-antitrypsin in capsaicin-receiving rats. Nitric oxide precursor L-arginine had a normalizing effect on reduced activity of alpha(1)-antitrypsin after capsaicin deafferentation. Our results suggest that nitric oxide has a modulatory effect on activity of proteinase inhibitors and is involved in the effector influence of capsaicin-sensitive nerves on alpha(1)-antitrypsin activity.

[Alternative changes of activity of alpha2-macroglobulin and alpha1-antitrypsin in rat blood following damage in capsaicin-sensitive nerves].

Effects of functional ablation of peptidergic sensory nerves with neurotoxic doses of capsaicin (150 mg/kg, s/c) as well as of their stimulation with small doses of capsaicin (5 mg/kg, i/p) on activity of proteinase inhibitors: alpha1-antitrypsin (alpha1-AT)-serine proteinase inhibitor and alpha2-macroglobulin (alpha2-MG)-nonspecific inhibitor were investigated in rat blood. The present results indicate alternative changes in activity of these proteinase inhibitors after damage of capsaicin-sensitive nerves: increasing decline in activity of alpha1-AT 1 and 3 or 14 days after administration of capsaicin and increase in activity of alpha2-MG land 3 day after the injection. The stimulation of afferent nerves with capsaicin did not change activity of the proteinase inhibitors 1 and 24 hours after the injection. It is suggested that the stable decrease in activity of alpha1-AT during a long period after the damage of capsaicin-sensitive nerves indicates an important role for these nerves in the regulating alpha1-AT that may exert a tonic effect on the activity alpha1-AT.

[Effect of damages of capsaicin-sensitive nerves on alpha1-antitrypsin activity in the rat blood]. / Vliianie povrezhdeniia kapsaitsin-chuvstvitel'nykh nervov na aktivnost' al'fa1-antitripsina v krovi krys.

Systemic administration of capsaicin (a neurotoxin of afferent nerves) in a dose of 150 mg/kg led to a decrease in the activity of alpha 1-antitrypsin (alpha 1-AT) in the blood of male Wistar rats. This effect is related to impairment of the local effector function of capsaicin-sensitive nerves in the liver, which is the main source of alpha 1-AT in the blood. Analogous results were obtained upon cutting of the hepatic branch of the vagus nerve involving capsaicin-sensitive afferent fibers of the liver.

[Comparative characteristic of serpin--alpha-1 proteinase inhibitor in human and mice serum]. / Sravnitel'naia kharakteristika serpina--alfa-1-proteinaznogo ingibitora syvorotki krovi cheloveka i myshei.

Serpin alpha-1-proteinase inhibitor have been studied in human subjects and in mice of different lines as acute phase reactant and during tumor development. In humans, there was no difference of serpin activity between men and women. Increased activity was noted in men with acute trauma (acute phase reaction). Comparatively to male, in female mice of different lines decreased activity of serum alpha-1-proteinase inhibitor, was shown. There was no increase of alpha-1-proteinase inhibitor activity during inflammation induced by zymosan administration in mice. alpha-1-proteinase inhibitor belongs to acute phase reactants in humans but not in mice; for mice alpha-2-macroglobulin is a more typical acute phase reactant as compared to alpha-1-proteinase inhibitor. Murine tumor development (hepatoma HA-1, lymphosarcoma LS, Lewis lung adenocarcinoma) was followed by a decreased activity of serum alpha-1-proteinase inhibitor both in successfully treated and untreated groups. According to data of literature, similar dated were obtained in humans with tumors. It was suggested that changes of expressiln of alpha-1-proteinase inhibitor by tumors and its secretion were involved in decreased activity of alpha-1-proteinase inhibitor.

Effects of stimulation of the trigeminal caudal nucleus on microvascular permeability in the eye in normal and capsaicin-treated rats.

Electrical stimulation of the trigeminal caudal nucleus in rats evoked increases in the permeability of eye microvessels. The microvascular effect did not appear when the nucleus was stimulated after administration of capsaicin 10 days before surgery (total dose 150 mg/kg, s.c., on two sequential days, given as 20, 30, 50, and 50 mg/kg). It is suggested that capsaicin-sensitive neurons in the trigeminal ganglion mediate the microvascular effect of stimulation of the trigeminal caudal nucleus.

[Effect of electrical stimulation of the trigeminal nucleus caudatus on the blood microvessel permeability in the eye in normal and capsaicin-treated rats]. / Vliianie élektrostimuliatsii troinichnogo kaudal'nogo iadra na pronitsaemost' mikrososudov v glazu u normal'nykh i podvergnutykh vozdeistviiu kapsaitsina krys.

Electrical stimulation of the trigeminal caudate nucleus increased permeability of the eye blood microvessels in rats. Ten days after capsaicin pre-treatment (total dose 150 mg/kg, s/c for 2 days: 20, 30, 50, 50 mg/kg) the electrical stimulation did not evoke any changes of the microvascular permeability in the eye. The data suggest that the effect of the stimulation is mediated through capsaicin-sensitive neurones of the trigeminal ganglion.

[Changes in the skin microvessel permeability following destruction of the mamillary-tegmental tract in normal and capsaicin-treated rats]. / Izmenenie pronitsaemosti mikrososudov kozhi u normal'nykh i obrabotannykh kapsaitsinom krys posle razrusheniia mamillo-tegmental'nykh putei.

An increase in vascular permeability as measured by the Evans Blue dye leakage into forepaws, was observed 1 hour following the destruction of mamillo-tegmental tracts in rats. Ten days after capsaicin pre-treatment the destruction did not induce any changes of the microvascular permeability in the skin forepaws. The findings suggest that the descending projections of hypothalamic mamillary nuclei might regulate the mechanisms of the skin microvessel permeability, the action being mediated through capsaicinsensitive neurons of the spinal ganglion.

Effect of electrical stimulation of the mamillary nuclei of the hypothalamus on skin vessel permeability in intact and capsaicin-treated rats.

Stimulation of the mamillary nuclei of the rat hypothalamus induced increases in the permeability of forelimb skin microvessels. This effect was not seen in rats stimulated after administration of capsaicin at a dose (150 mg/kg) sufficient to deplete vasoactive neuropeptides from the peripheral nerve terminals of capsaicin-sensitive neurons. These data indicate a role for the mamillary nuclei in central mechanisms modulating the effector functions of primary capsaicin-sensitive neurons.

[A change in the permeability of eye microvasculature during damage to the hypothalamic nuclei in intact and rats and rats pretreated with capsaicin]. / Izmenenie pronitsaemosti mikrososudov glaza pri povrezhdenii iader gipotalamusa u intaktnykh i predvaritel'no obrabotannykh kapsaitsinom krys.

The destruction of rat hypothalamic mamillary nuclei causes impaired permeability of eye microvessels receiving afferent innervation from the trigeminal ganglion. This effect was eliminated by pre-treatment of the animals with capsaicin (200 mg/kg), which exhausted the content of substance P and calcitonin-gene-specific peptide, from the primary capsaicin-sensitive neurons of trigeminal and spinal ganglia. The findings show that the peripheral effect caused by the destruction of mamillary nuclei is mediated through capsaicin-sensitive neurons of the trigeminal ganglion.

Effect of lesion of the hypothalamic mamillary nuclei on skin blood vessel permeability in normal and capsaicin-pretreated rats.

Contralateral increased exudation of plasma proteins, as measured by Evans Blue leakage into the fore paws, was produced by unilateral electrocoagulation of the mamillary nuclei in rats. Ten days after adult capsaicin pretreatment (increasing doses/4 days total 200 mg/kg, s.c.) the unilateral destruction of these nuclei did not evoke any changes of skin blood vessel permeability in both contralateral and unilateral paws. The findings show that the central nervous system may modulate the capsaicin-sensitive peptidergic neuron action on blood vessel permeability.

[The role of leukocytic infiltration in the development of neurogenic processes in the denervated rat cornea]. / Rol' leikotsitarnoi infil'tratsii v razvitii neirogennykh protsessov v denervirovannoi rogovitse krys.

In early and late stages after different types of deafferentation of rat cornea extents of leukocyte infiltration and pathological changes are variable. Change of thickness of anterior epithelium and substantia propria, stratification of substantia propria fibres as well as epitheliocyte death and erosion occur only at late time intervals of deafferentation (after 1 d) when a large number of leukocytes appear in cornea. One day after the deafferentation performed following preliminary leukopoiesis suppression by irradiation, single leukocytes are encountered only in substantia propria of cornea while anterior epithelium thickness does not differ from that of intact animals, and the extent of pathological changes in substantia propria is reduced. These data demonstrate polymorphonuclear leukocyte participation in the development of neurogenic dystrophia in cornea.

[The effect of electrostimulation of the hypothalamic mamillary nuclei on the vascular permeability of the skin in intact and capsaicin-pretreated rats]. / Vliianie élektrostimuliatsii mamilliarnykh iader gipotalamusa na pronitsaemost' sosudov kozhi u intaktnykh i predvaritel'no obrabotannykh kapsaitsinom krys.

Electrical stimulation of the hypothalamic mamillary nuclei increased the permeability of the skin blood vessels in rats. Pretreatment of the animals with capsaicin prevented the effect. The mamillary nuclei seem to take part in the central mechanisms of efferent function of the capsaicin-sensitive neurons.