Response of the cerebral vessels to noradrenalin during hypocapnia and inhibition of prostaglandin biosynthesis

Hypocapnia caused by forced hyperventilation appreciably reduces the pressor action of noradrenalin on the cerebral vessels and lowers the arterial pressure. When prostaglandin biosynthesis is inhibited by indomethacin while hypocapnia continues, injection of noradrenalin into the brain vessels is accompanied by a marked increase in the cerebrovascular resistance and in the arterial pressure. It is concluded that prostaglandins play an important role in the mechanism of autoregulation of the cerebral circulation and, in particular, under conditions of adrenergic stimulation and hypocapnia.Department of Pharmacology and Problem Laboratory for Pharmacology of the Cardiovascular System, Erevan Medical Institute.(Presented by Academician of the Academy of Medical Sciences of the USSR, V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditssiny, Vol. 81, No. 6, pp. 643–645, June, 1976.     

Unequal sensitivity of the arterial systems of the brain to noradrenalin

An investigation on unanesthetized and anesthetized cats showed that noradrenalin acts directly on the brain vessels and increases their tone. Noradrenalin was also found to affect blood vessels of the different arterial systems of the brain unequally: It raised the perfusion pressure in the system of the carotid arteries more than in the vertebral arterial system.Laboratory of Pharmacology of the Cardiovascular System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 1, pp. 47–49, January, 1976.     

Effect of ethimizole on changes in brain metabolism caused by overstimulation

During overstimulation (electrical stimulation for 3 h) of rats considerable changes are observed in their brain metabolism. These changes are manifested as exhaustion of the noradrenalin reserves and disturbance of energy metabolism, leading to a fall in the creatine phosphate level. Preliminary (before electrical stimulation) administration of ethimizole prevented the noradrenalin and creatine phosphate deficiencies in the brain tissue of the overstimulated animals.Laboratory of Experimental Pharmacology, Department of Pharmacology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 299–301, March, 1978.     

Effect of phentolamine on the cerebral circulation

The effect of phentolamine on the volume velocity of the cerebral blood flow, tone of the cerebral vessels, and partial pressure of oxygen in the brain tissue was studied in acute experiments on anesthetized and unanesthetized cats. Intravenous injection of phentolamine led to a prolonged fall of blood pressure and of the tone of the intracranial and, to a lesser degree, the extracranial vessels. The volume velocity of the cerebral blood flow was reduced in animals with marked phentolamine hypotension.If the perfusion pressure was stabilized, the blood flow was increased. Changes in pO₂ in the brain tissue corresponded largely to the blood flow. Preliminary atropinization and denervation of the carotid zones did not alter the effect of phentolamine. Phentolamine reduced or abolished the constrictor action of noradrenalin and phenylephrine on the brain vessels.Department of Pharmacology, Pyatigorsk Pharmaceutical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 309–311, September, 1977.     

Effect of neurogenic injury to the myocardium on activity of some enzymes of its energy metabolism

After electrical stimulation of the arch of the aorta in rabbits for 3 h exhaustion of the tissue noradrenalin (NA) reserves in the myocardium was accompanied by an increase in the activity of hexokinase (HK), lactate dehydrogenase (LD), and glucose-6 phosphate dehydrogenase (G6PD). Injection of L-Dopa after electrical stimulation prevented the fall of the NA level in the heart muscle and the change in activity of the above enzymes. The results confirm the important role of disturbances of mediator metabolism in mechanisms of development of metabolic and generative injuries.Laboratory of Experimental Pharmacology, Department of Pharmacology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 10, pp. 1205–1206, October, 1976.     

Effect of malaben on catecholamine content in organs of animals with experimental myocardial infarction

The content of adrenalin and noradrenalin was determined in tissues of the heart, adrenals, spleen, and brain of rats with experimental myocardial infarction. A considerable fall in the tissue catecholamine level was found. Malaben restores the normal catecholamine content in the tissues in myocardial infarction, posibly as a result of the antihitamine properties of the compound.Department of Pharmacology, Leningrad Institute of Pharmaceutical Chemistry. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 7, pp. 49–51, July, 1977.     

Effect of neurogenic injury to the heart on its glucose-6-phosphate dehydrogenase content

Neurogenic damage to the rat heart muscle by electrical stimulation of the arch of the aorta leads to the development of a deficiency of tissue noradrenalin (NA), the mediator of the sympathetic nervous system. This is accompanied by a marked increase in glucose-6-phosphate dehydrogenase (G6PD) activity. Preliminary administration of actinomycin D, an inhibitor of RNA synthesis, completely prevents the increase in G6PD activity in the heart muscle tissue following neurogenic injury. The results indicate the more rapid induction of this enzyme in the tissue of the myocardium after neurogenic injury, which correlate with changes in the tissue NA balance.Laboratory of Experimental Pharmacology, Department of Pharmacology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anishkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 9, pp. 297–298, September, 1978.     

Responses of the cerebral blood flow to hypo-and hypercapnia after inhibition of prostaglandin biosynthesis by indomethacin

Quantitative investigation of the local cerebral blood flow by the hydrogen clearance method and of the blood flow into the brain by means of an electromagnetic flowmeter showed that inhibition of prostaglandin biosynthesis by indomethacin inhibits the response of the cerebral vessels to hypercapnia, whereas the effects of hypocapnia are not only preserved but are actually enhanced. This difference in the response of the brain vessels to hypo- and hypercapnia during inhibition of prostaglandin biosynthesis suggests that effects of hyper- and hypocapnia are produced by different mechanisms. It is postulated that a decrease in the prostaglandin concentration reduces the sensitivity of the brain vessels to hypercapnia and increases their sensitivity to hypocapnia.Problem Laboratory for Pharmacology of the Cardiovascular System, Department of Pharmacology, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 3, pp. 240–243, March, 1979.     

Effect of carbidine on content and deposition of adrenergic neurotransmitter in synaptic vesicles

The effect of the original Soviet psychotropic agent carbidine on the content and deposition of adrenergic mediator in the synaptic vesicles of sympathetic nerve fibers of the rat vas deferens was studied by electron-microscopic cytochemistry. The results showed that carbidine can reduce the reserves of monoamines deposited in synaptic vesicles but does not affect the uptake and accumulation of exogenous noradrenalin by synaptic vesicles.Group for Electron Microscopy, Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 80, No. 10, pp. 69–72, October, 1975.     

Role of prostaglandins in the regulation of catecholamine uptake by the myocardium

The study of the effect of prostaglandin E₁ (PG-E₁) on catecholamine uptake by homogenates of albino rat myocardium showed that in concentrations of 2×10^–6M PG-E₁ considerably inhibits the uptake of adrenalin and causes some decrease in the uptake of noradrenalin by the heart muscle. Neither PG-E₁ nor PG-A₁ (in concentrations of between 2×10^–10 and 2×10^–6M) had any effect on interaction between troponin and noradrenalin: The intensity of luminescence of troponin in the presence of noradrenalin was unchanged on the addition of PG-E₁ and PG-A₁. The ability of PG to reduce catecholamine uptake by the myocardium is not due to its effect on the interaction between troponin and catecholamines, but depends on different mechanisms.Department of Pharmacology, Erevan Medical Institute. Laboratory of Molecular Cardiology, Institute of Cardiology, Mininistry of Health of the Armenian SSR, Erevan. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 7, pp. 44–45, July, 1978.     

Effect of hydiphen on behavior and hemodynamic manifestations of emotional stress

Hydiphen is an original Soviet tranquilizer (diphenylphosphinylacetic acid hydrazide). In a dose of 120–150 mg/kg hydiphen restores the central baroreceptor reflex regulation of arterial pressure, when depressed in cats during an acute emotional-stress reaction (confrontation with a dog). The compound has an antihypertensive antiaggressive action, and does not induce ataxia. Behavior was investigated quantitatively in animals during group interaction, using a five-point system.Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Department of Pharmacology, First Leningrad Medical Institute. Department of Pharmacology, S. V. Kurashov Kazan' Medical Institute, Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 310–312, March, 1980.     

Effect of noradrenalin on endogenous prostaglandin E and F2α production in cerebral and extracranial vessels of cats

The production of prostaglandins (PG) E and F₂ in the isolated cerebral and extracranial vessels of cats was determined quantitatively. Basal PG production was found to be greater in the cerebral vessels, and PGF₂ exceeded PGE. On incubation of isolated vessels with noradrenalin, production of vasopressor PGF₂ was reduced, and this was accompanied by a considerable increase in the content of vasopressor PGE. The difference was particularly marked in the cerebral vessels. The level of endogenous PG production by the cerebral vessels, it can tentatively be suggested, has an important role for the local regulation of vascular tone, and a disturbance of their dynamic ratio may be one cause of the development of cerebrovascular pathology.Problem Laboratory on Pharmacology of the Cardiovascular System, Department of Pharmacology, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 422–423, October, 1979.     

Effect of methylapogalanthamine on tone of the cerebral,extracranial, and peripheral vessels

Acute resistographic experiments on anesthetized and unanesthetized cats showed that methylapogalanthamine lowers the general arterial pressure and the tone of the cerebral, extracranial, and femoral vessels. The effect on the femoral vessels is the strongest. A biphasic (dilator-constrictor) response was frequently observed. Methylapogalanthamine weakened the constrictor response of the intra- and extracranial vessels to stimulation of the cervical sympathetic nerve. Anesthesia potentiated, whereas rausedil weakened the vasodilator effect of methylapogalanthamine.Department of Pharmacology, Pyatigorsk Pharmaceutical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éxperimental'noi Biologii i Meditsiny, Vol. 86, No. 10, pp. 438–441, October, 1978.     

Activation of tyrosine hydroxylase during electrical stimulation of isolated nerve endings of the rat hypothalamus

The effect of electrical stimulation on synaptosomal membrane-bound tyrosine hydroxylase (TH) activity in the rat hypothalamus was investigated. Electrical stimulation intensified respiration and glycolysis, evidence of excitation of the synaptosomes. Against this background, activity of membrane-bound TH was increased. The value of K_m for tyrosine fell from 0.091 to 0.026 mM. Inhibition of the enzyme activity by the end product of cathecholamine biosynthesis (noradrenalin) was reduced. It is postulated that the effect of depolarization on the rate of catecholamine synthesis in nerve endings is effected through modification of TH.Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Academy of Medical Sciences of the USSR. Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 543–545, May, 1977.     

Effect of type E prostaglandins on changes in cerebrovascular resistance and arterial pressure produced by tyramine

Investigation of the cerebrovascular resistance and arterial blood pressure by resistography showed that type E prostaglandins inhibit the pressor action of tyramine on the cerebral vessels and on the blood pressure. Indomethacin, which inhibits prostaglandin biosynthesis, delayed the development of tachyphylaxis to tyramine and restored its pressor effect. Iproniazid, a monoamine oxidase inhibitor, did not affect the rate of development of tyramine tachyphylaxis following administration of indomethacin but potentiated the pressor effect of tyramine. It is suggested that the effect of indomethacin on the pressor effect of tyramine is based on increased sensitivity of the vascular adrenoreceptors.Problem Laboratory for Pharmacology of the Cardiovascular System, Department of Pharmacology Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 307–310, March, 1978.     

Interaction between nonachlazine and noradrenalin on a model phospholipid membrane

The binding of nonachlazine (NON), imipramine (IMI), and noradrenalin (NA) with model phospholipid membrane vesicles (liposomes) was investigated. Binding was determined by the quenching effect of these substances on a 3-methoxybenzanthrone (MBA) fluorescent probe present in the membrane. The method of calculating the parameters of binding of the substances with the membrane based on a change in intensity of fluorescence of MBA was developed. The binding constants of NON, IMI, and NA, with the membrane were (4.3±10.3)·10³ M^–1, (2.7±0.2)·10³ M^–1, and (0.7±0.15)·10³ M^–1 respectively. NON and IMI were shown to be able to compete with NA for the binding sites. These competitive interactions can be regarded as the probable mechanism of the blocking of reverse NA transport through the axonal and vesicular membranes characteristic of NON and IMI.Laboratory of Pharmacology of the Cardiovascular System, Institute of Pharmacology, Academy of Medical Sciences of the USSR. Department of Biophysics, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1084–1086, September, 1976.     

Changes in prostagladin E levels in arterial blood and cerebrospinal fluid during hypo-and hypercapnia

A considerable increase was found in the concentration of prostaglandins of type E (PGE) in the CSF and arterial blood of cats during hypocapnia for 3 min. During hypocapnia for 30 min the original PGE level was restored. During hypercapnia for 3 min the PGE concentration was increased in the CSF compared with the control, but reduced in the arterial blood. After hypercapnia for 30 min the PGE concentration in the CSF and blood was reduced below its level after 3 min, and later it fell below the basal level. It is suggested that during hypocapnia PGE limit its constrictor effect on the cerebral vessels, whereas during hypercapnia they facilitate the response of the vessels to CO₂.Problem Laboratory for Pharmacology of the Cardiovascular System, Department of Pharmacology, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 9, pp. 309–311, September, 1979.     

Effect of blocking neuronal and extraneuronal uptake of bioamines on the adrenosensitizing action of tricyclic antidepressants

Experiments on isolated intact, and also denervated, vasa deferentia of rats showed that tricyclic antidepressants (melpiramine, noveril, azaphen), in low concentrations (1·10^–9 g/ml), like cocaine (1·10^–5 g/ml), have an aminopotentiating action. Denervation followed by blocking of extraneuronal uptake of the amine by deoxycorticosterone (1·10^–5 g/ml) did not change the position, shape, or slope of the concentration-effect curves of noradrenalin obtained in the presence of noveril and cocaine. It is postulated that the mechanism of the adrenosensitizing action of tricyclic antidepressants on smooth-muscle organs is predominantly postsynaptic.Department of Pharmacology, Medical Institute, Donetsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 5, pp. 556–558, May, 1976.     

Ventral hippocampal mediator mechanisms in anxiety states formed by various aversive situations

Department of Pharmacology, M. Gor'kii Donetsk State Medical Institute. (Presented by Academician of the Russian Academy of Medical Sciences K. V. Sudakov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 10, pp. 374–376, October, 1992.     

Effect of 5-HT1A receptor agonists on amino acid- and dopaminergic responses of neurons

Department of General and Clinical Pharmacology, M. Gor'kii Donetsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR P. V. Sergeev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 12, pp. 609–610, December, 1991.