[Fur color gene profiles and length of hair of several cat populations in Cuba, Costa Rica, Colombia, Paraguay, Chile and Argentina, and possible genetic origins of these cat populations]. / Raspredelenie genov okraski i dliny shersti v populiatsiiakh koshek Kuby, Kosta-Riki, Kolumbii, Paragvaia, Chili i Argentiny i vozmozhnoe proiskhozhdenie étikh populiatsii.

Until the present moment, only a scarce number of Latin American domestic cat populations have been studied from a population genetic standpoint. For this reason, the cat populations of La Havana (Cuba), San José (Costa Rica), Bogota and Ibagué (Colombia), Asuncion (Paraguay), Santiago (Chile) and Buenos Aires (Argentina) were sampled for several coat genes. The results obtained were as follows: (1) there was a strong genetic resemblance between several Hispanic American cat populations (especially, those of Buenos Aires, San José and the two Colombian populations studied) and those from South Western United States (California, Texas and Colorado), which adds support to the suspicion that these populations probably have a common origin; (2) The cat population of Santiago (Chile), contrarily to the other Hispanic American populations studied, showed a strong genetic resemblance with some Anglo North American populations; and (3) The l (long hair) and d (dilution) alleles showed systematic higher frequencies in the Hispanic American populations than those observed in Spain. Although the Hispanic American populations were not identical to the current Spanish populations (with the exception of Asuncion), this historic genetic experiment was very different to that found for the British populations and their overseas colonies.

Treadmill exercise-induced stress causes a rise of blood histamine in normotensive but not in primary hypertensive humans.

We have previously shown an interaction between noradrenergic and histamine-containing neurons in the rat vas deferens. As a generalized phenomenon, this interaction is involved in a novel peripheral reflex that, in an inhibitory way, modulates sympathetic activity and arterial pressure. Consistent with this, an activation of postganglionic sympathetic neurons causes a rise in rat blood histamine. In the present study, we showed that enhanced sympathetic activity due to treadmill exercise in normotensive humans, is accompanied by a rise in blood histamine, suggesting the presence of a similar neuronal interaction in humans. In contrast, the rise in blood histamine does not occur in primary hypertensive humans during the same degree of physical exercise, suggesting that this interaction is faulty in such hypertensives and could be involved in the pathophysiology of the disease.

Footshock-induced rise of rat blood histamine depends upon the activation of postganglionic sympathetic neurons.

We have previously shown the existence of a novel peripheral reflex inhibitorily modulating the vas deferens sympathetic activity. An interaction between noradrenergic and histamine-containing neurons is involved in this reflex. As an overall mechanism of sympathetic autoregulation, we found that enhanced sympathetic activity in the rat during the stress induced by brief inescapable footshocks caused a marked rise of blood histamine that was seemingly dependent upon sympathetic activity. This rise was prevented by either previous ganglionic blockade with hexamethonium or chronic guanethidine-induced sympathectomy. Previous adrenal demedullation did not impair this rise. Thus, it appears that only the sympathetic postganglionic neuron, interacting with a histamine-containing neuron, is involved in the rise of blood histamine induced by footshocks.

Thioperamide, a histamine H3-receptor blocker, facilitates vasopressor response to footshocks.

OBJECTIVE AND DESIGN: We assessed the functional role of the histamine H3-receptor in conscious intact rats during activation of the sympathoadrenal axis. MATERIAL: Male Sprague-Dawley rats, with or without cerebroventricular cannula, were subjected to mild footshocks and mean arterial pressure (MAP) and heart rate were determined using a tail-cuff plethysmograph. TREATMENTS: Saline, phentolamine (3 mg/kg, i.p.), (R)-alphafluoromethylhistidine (AFMH) (100 mg/kg, i.p., or 100 microg/5 microl, i.v.t.), (R)-alphamethylhistamine (AMH) (2 mg/kg, i.p. or 100 microg/5 microl, i.v.t.), thioperamide (THIO) (1 or 2 mg/kg, i.p., or 100 microg/5 microl, i.v.t.), mepyramine (10 mg/kg, i.p.), cimetidine (2 mg/kg, i.p.). METHODS: Urinary catecholamines were determined by fluorometry. Statistical differences between experimental groups were evaluated by Student's t-test or one-way ANOVA. RESULTS: Footshocks increased both MAP and heart rate. The vasopressor response to footshocks was facilitated (p < 0.001) by i.p. administration of AFMH, a histidine decarboxylase inhibitor, or THIO, a H3-receptor antagonist, but not by i.v.t. injection of these drugs. AMH, a H3-receptor agonist, given i.p., decreased the vasopressor response to footshocks (p < 0.001). This action of AMH was abolished by THIO but not by mepyramine or cimetidine. The MAP response to exogenous norepinephrine was not altered by i.p. administration of either AFMH or THIO. CONCLUSIONS: Our results demonstrate an involvement of peripheral histamine H3 prejunctional receptors in the inhibitory modulation of peripheral noradrenergic responses during stress.

Alpha-fluoromethylhistidine, an inhibitor of histamine biosynthesis, causes arterial hypertension.

In this study we assessed the cardiovascular response to 13 days of irreversible inhibition of the enzyme histidine-decarboxylase (HD) with alpha-fluoro-methylhistidine (AFMH). Age-matched untreated rats were used as controls, Tail-cuff mean arterial pressure (MAP) and heart rate (HR) rose progressively in AFMH-treated rats, reaching maximal values during the study period by the 13th day of treatment. There was a reduction in urinary histamine at the day 7 and 13, and of sodium excretion at the day 7 of treatment, while the renal catecholamine excretion was increased at both days of treatment, suggesting an increase of sympathetic activity. At the 13th day of treatment, there was an activation of the renin-angiotensin-aldosterone system. In addition, the cardiovascular responses to footshock stress were determined in rats treated intraperitoneally (i.p.) or intracerebroventricularly (i.v.t.) with a single dose of AFMH. Peripheral sympathetic facilitation was found, as the hemodynamic response to footshock stress was significantly enhanced after i.p. administration, but not after i.v.t. administration of AFMH. Our results suggest that conditions of peripheral histamine deficiency may result in sympathetic facilitation, arterial hypertension and tachycardia in the rat.

Interaction between noradrenergic and histamine-containing neurons in the rat vas deferens.

A decussation of histamine (HA)-containing nervous pathways, at the level of the sympathetic ganglionic clusters of the rat vas deferens, was formerly described in this laboratory. This type of neuronal distribution is confirmed in the present study by using surgical interruptions of nervous pathways and determining changes in L-histidine decarboxylase (HD) activity, as an HA-containing neuron marker, after nerve degeneration. Decreases of HD activity follow previously found decreases of HA levels in the vas deferens submitted to the same type of surgical interruptions. An interaction between noradrenergic neurons and HA-containing neurons is suggested, because electrical stimulation of the preganglionic sympathetic nerve causes a rapid increase in HD activity in the ipsilateral vas deferens, possibly as a signal of the activation of HA-containing neurons, whose pathways come from the opposite ganglion. This activation appears to be indirect, presumably through a sensory interneuron, which upon being excited by the enhanced sympathetic discharge crosses over to stimulate the contralateral ganglionic HA-containing neuron. The sympathetic discharge-induced peripheral loop reflex resulting in an increase in HD activity depends upon the integrity of the noradrenergic neuron. An, as yet unknown, interaction seems to occur between the noradrenergic neurons and the HA-containing neurons in the rat vas deferens, when the sympathetic activity of the latter is enhanced.

Two models of peripheral sympathetic autoregulation: role of neuronal histamine.

We have studied the influence of a peripheral histamine-containing neuronal system on the sympathetic activity of the rat vas deferens. Chronic surgical interruptions of the sympathetic structures involving the adjacent histamine-containing neuronal system cause changes of sympathetic activity, as measured by the rate of disappearance of norepinephrine after reserpine administration to the awake rat. Sympathetic ganglionectomy performed on either side causes an enhancement of the sympathetic activity in the contralateral vas deferens. When the decussation of histamine-containing pathways is surgically interrupted (interganglionic section), a bilateral enhancement of sympathetic activity occurs. The histamine-containing neuronal system seems to exert a contralateral reciprocal inhibitory modulation of sympathetic activity at the vas deferens. This modulation is evoked by nervous impulses traveling in the preganglionic fiber because enhancement of sympathetic activity due to contralateral ganglionectomy is suppressed by ipsilateral decentralization. No compensatory reflexes of central origin are observed. Sympathetic enhancement due to interruption of histamine-containing nervous pathways is reversed by i.v. infusion of histamine. An H-1 or H-2 histamine receptor antagonist does not have any effect on the vas deferens sympathetic activity of the intact rat. In the heart of the deafferentated dog, removal of the left stellate sympathetic ganglion causes facilitation of the chronotropic responses induced by stimulation of the right sympathetic postganglionic nerve, also suggesting a peripheral contralateral inhibitory modulation of sympathetic activity at the heart. It appears from all these findings that a peripheral inhibitory reflex is evoked when sympathetic activity is enhanced, thus contributing to maintaining homeostasis.

[Effect of cerebral noradrenaline and dopamine depletion on spontaneous and amphetamine-stimulated motor activity in rats]. / Efecto del agotamiento de la noradrenalina y dopamina cerebrales de la rata sobre la actividad locomotriz espontanea y la estimulada por anfetamina.

Selective depletion of rat brain noradrenaline and dopamine by 6-hydroxidopamine, 30-60 days after cisterna magna microinjection, reduced nocturnal spontaneous locomotor activity by 40%. This treatment also reduced by 90% the excitatory effect of amphetamine on locomotion. Disulfiram and FLA-63, selective inhibitors of dopamine-B-hydroxilase, depleted by 70% the noradrenaline content of striatum and brain cortex, without changes of dopamine concentration in the same areas. These rats showed a reduced spontaneous locomotor activity and a blockade of amphetamine stimulating activity. In conclusion, our results give support to the hypothesis of brain noradrenaline having a major role on the control of locomotor activity of rodents.

A possible crossed histamine-containing pathway adjacent to the sympathetic system of the rat vas deferens.

Studies using nerve degeneration techniques (ganglionectomy, interganglionic section, postganglionic axotomy, uni- or bilateral hypogastric nerve section and right pelvic ganglionectomy) and fluorometric determinations of histamine and norepinephrine have shown the presence of nervous pathways containing histamine adjacent to the sympathetic system of the rat vas deferens. The findings suggest that these pathways cross between the ganglionic clusters located at the angle formed by the seminal vesicle and the vas deferens. They are not structurally related to the central nervous system by way of the hypogastric or pelvic ganglion. The histamine-containing pathways are independent of the noradrenergic pathways as dissociation between norepinephrine depletion and histamine depletion can be shown under nerve degeneration. The time course of nerve degeneration over a long period after sympathectomy shows a biphasic effect on histamine levels of the vas deferens. The early histamine depletion would be indicative of degeneration of histamine-containing pathways, and the delayed histamine increasing phase has been considered as due to accumulation of mast cells in the degenerating nerve sheaths. A possible role for the histamine-containing pathways in the modulation of sympathetic activity is envisaged.

Cholinergic manipulations in the rat basolateral amygdaloid nucleus on locomotor activity induced by amphetamine.

Microinjections of cholinergic antagonists in the vicinity of the basolateral amygdaloid nucleus produced a marked reduction of amphetamine-induced hyperactivity when amphetamine was administered i.p. in relatively large doses (1.5 mg/kg). Cholinergic agonists enhanced locomotor activity induced by relatively small doses of amphetamine (0.5 mg/kg). These observations suggest that cholinergic activity in the amygdala modulates the locomotor response to amphetamine.

An in vivo cholinergic influence on the retention of [3H]noradrenaline in regional brain synaptosomes.

Rats were intraventricularly (icv) injected with [3H]noradrenaline and the retention of the amine was determined in synaptosomes obtained from cerebral cortex, hypothalamus and brain stem. Previous icv administration of hemicholinium-3, effective enough to markedly decrease brain acetylcholine levels, increased the retention of synaptosomal [3H]noradrenaline in hypothalamus and cerebral cortex; this increased retention did not occur in the brain stem. The increased retention of [3H]noradrenaline, produced by hemicholinium-3, was reversed by a concomitant icv dose of choline, which in turn reversed the decrease of acetylcholine caused by hemicholinium-3. These results are interpreted as brain cholinergic activity having an influence on the turnover of noradrenaline in some brain regions.

In situ noradrenaline-induced stimulation of dog thyrotrophic secretion.

Anterior pituitary microinfusions of noradrenaline in the dog causes a significant release of TSH while adrenaline and dopamine do not.

Effects of hemicholinium-3 or physostigmine on rat brain noradrenaline depletion induced by foot shocks.

Foot shocks applied to the rat on a grid floor caused brain noradrenaline depletion. Hemicholinium-3 injected intracerebroventricularly (i.c.v.) blocked the noradrenaline depletion and this blockade was reversed by choline (i.c.v.). Physostigmine (i.c.v.) had different effects according to the age of the rats: "young" and "intermediate" groups were depleted but not "adult" groups. Physostigmine plus shocks caused depletion only in "young" groups; the depletion not shown in "intermediat" groups, reappeared after pretreatment with alpha-methyl-p-tyrosine. It is concluded that there probably is a relationship between cholinergic and adrenergic neural systems when brain noradrenaline id depleted by shocks.

Presence of serotonin in the rat vas deferens: its influence on contractile responses.

Serotonin has been detected in the rat vas deferens. Increase in the serotonin concentration by exposure of the rat vas deferens to L-tryptophan occurs in vitro. p-chlorophenylalanine partly blocks the increase in serotonin concentration induced by tryptophan in vitro but not in vivo. Chronic sympathetic denervation induces an increase in 5-HT concentration. Responses of the vas deferens to transmural stimulation are depressed by pretreatment of rats with p-chlorophenylalanine, and the depression is reversed by incubation in vitro with 5-hydroxytryptophan or serotonin. Serotonin can enhance the response to transmural stimulation at low concentrations but has no effect at higher concentrations. Physostigmine-induced enhancement of the response to stimulation is depressed only by higher concentrations of serotonin. The results raise the question whether endogenous serotonin can act as a modulator of neurotransmission in the rat vas deferens.

PIP: Various experiments were conducted to evaluate the influence of serotonin (5-HT) on contractile responses of the rat vas deferens in vitro and in vivo. In vitro exposure of the vas deferens to L-tryptophan increased serotonin concentration. p-Chlorophenylalanine partially blocked this increase in vitro but not in vivo. The concentration of 5-HT was also increased by chronic sympathetic denervation. Pretreatment with p-chlorophenylalanine depressed the contractile response to transmural stimulation, while incubation with 5-hydroxytryptophan or serotonin reversed this effect. Low, but not high, concentrations of serotonin enhanced the response to transmural stimulation. However, only high concentrations of serotonin depressed the physostigmine-induced enhancement of the contractile response to transmural stimulation. The results suggest that endogenous serotonin may modulate neurotransmission in the rat vas deferens.

Action of cocaine and chronic sympathetic denervation on vagal escape.

1. The effect of cocaine has been studied on vagal escape and on the tachycardia due to vagal stimulation in the atropinized dog. All the dogs were submitted to acute cervical section of the spinal cord and acute or chronic sympathetic denervation.2. Cocaine, 5 mg/kg or 40 mug/kg/min, I.V., induces a significant enhancement of the ventricular escape. The effects of a continuous infusion of cocaine are more reproducible than those of a single injection of the drug.3. Cocaine, 40 mug/kg/min, I.V., potentiates the tachycardia due to vagal stimulation in the atropinized dog.4. Chronic thoracic sympathectomy markedly retards the recovery of the ventricular rate from the inhibitory action of the vagus. Under this condition, the infusion of cocaine does not significantly enhance the ventricular escape.5. These findings suggest that an adrenergic mechanism located at the sympathetic nerves supplying the heart is substantially involved in the phenomenon of vagal escape.