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Biomedical subjects

J M Saavedra

Publications and source records attributed to J M Saavedra.

At least 19 recordsLinked to original sources

Brain catecholamines during development of DOCA-salt hypertension in rats.

The activity of the adrenaline-forming enzyme, phenylethanolamine-N-methyltransferase (PNMT) and the levels of the catecholamines dopamine, noradrenaline and adrenaline were determined during the development of the DOCA-salt hypertension in selective areas of the rat brain stem and hypothalamus. Increases in PNMT activity were restricted to the A1 area and locus coeruleus after 2 weeks of DOCA-salt treatment and were extended to the A2 area after 9 weeks of treatment. Adrenaline concentrations were higher in these areas only after 9 weeks of treatment. Noradrenaline levels did not change, except in the nucleus tractus commissuralis. Dopamine levels were unchanged at all times and in all structures studied. These results implicate brain stem adrenaline neurons in the central response which occurs during the DOCA-salt experimental hypertension.

Animals

Estrogen-induced efflux of endogenous catecholamines from the hypothalamus in vitro.

Short-term organ cultures of the intact hypothalamus were used to study the effects of various estrogenic compounds on catecholamine release. Estradiol-17 beta (0.1--20 microM) produced a concentration-dependent efflux of norepinephrine and dopamine while its biologically inactive enantiomer, estradiol-17 alpha, was ineffective at concentrations up to 20 microM. Diethylstilbestrol, a potent non-steroidal estrogen, was as effective as estradiol-17 beta in inducing catecholamine efflux. In contrast, weakly or non-estrogenic steroids such as estrone, estriol, and corticosterone were without effect. The time course of the estrogen-induced efflux of hypothalamic catecholamines was similar to that previously reported for the estrogen-induced accumulation of hypothalamic cAMP, providing further evidence for the involvement of catecholamines in this effect. Theses results suggest that estrogen may facilitate the release of catecholamines within the hypothalamus.

Animals

Adrenaline levels in brain stem nuclei and effects of a PNMT inhibitor on spontaneously hypertensive rats.

The adrenaline content of specific brain stem areas was decreased in young (4 week-old) but not in adult (14 week-old) SHR. Some of these areas also showed increased PNMT activity, indicating a possible enhanced release or metabolism of adrenaline early in the development of the hypertension. Dopamine and noradrenaline levels, on the contrary, were not changed either in young or adult animals. Administration of a PNMT inhibitor to adult SHR resulted in a decrease of the blood pressure in SHR to control levels. These observations support the hypothesis of a participation of adrenergic mechanisms in the development of genetic hypertension, and indicate the possibility for the use of PNMT inhibitors as hypotensive agents.

Animals

Adrenaline, noradrenaline and dopamine levels in specific brain stem areas of acutely immobilized rats.

Catecholamines (adrenaline, noradrenaline and dopamine) have been measured in specific areas of the rat brain stem after acute immobilization stress. Adrenaline levels were significantly decreased after 240 min of immobilization in all areas studied: A1 area, nucleus commissuralis (NCO), A2 area, anterior part of the nucleus tractus solitarii (NTS), and the locus coeruleus. Noradrenaline concentrations in stressed rats were significantly reduced only in the NTS area. In contrast, during stress there were no significant changes in dopamine concentrations with respect to control values in any of the areas studied. These results implicate the participation of central adrenaline neurons, localized in specific brain stem areas, and noradrenaline neurons innervating the rostral part of the nucleus tractus solitarii, in the mechanism of central response to acute stress.

Animals

Biochemical changes accompanying unilateral 6-hydroxydopamine lesions in the rat substantia nigra.

The biochemical consequences of a unilateral 6-hydroxydopamine injection into the substantia nigra of the rat brain were investigated. Projections of dopaminergic neurons from the A8-A9-A10 regions to a number of forebrain areas were confirmed. No innervation to the hypothalamus, including the median eminence, or to the brain stem, could be found with the present techniques. No destruction of serotonergic or GABAergic fibers could be demonstrated in the lesioned substantia nigra. Increases in glutamic acid decarboxylase activity were found restricted to the caudate and zona compacta of the substantia nigra ipsilateral to the lesion, indicating the possibility of a physiological interaction between GABAergic and dopaminergic systems. The neuroanatomical localization of the nigral dopamine-sensitive adenylate cyclase was also studied. No change in enzyme activity was found after destruction of a great proportion of the dopaminergic cells, suggesting that this enzyme has an extradopaminergic localization in the substantia nigra.

Adenylyl Cyclases

Changes in central catecholaminergic neurons in the spontaneously (genetic) hypertensive rat.

Catecholamines and catecholamine-synthesizing enzymes have been examined in specific brain areas during the development of spontaneously (genetic) hypertensive (SH) rats. Changes in catecholamine metabolism were localized to regions of the brain implicated in the regulation of blood pressure. Norepinephrine levels and dopamine-beta-hydroxylase (DBH) activities were decreased in specific nuclei of the hypothalamus and in the nucleus interstitialis striae terminalis ventralis, in both young and adult rats. The decrease in the formation of norepinephrine can result in a reduced activation of central alpha-adrenergic receptors which may be related causally to the onset of hypertension. The activity of the epinephrine-forming enzyme, phenylethanolamine-N-methyltransferase (PNMT), was increased in the A1 and A2 areas of the brainstem in young SH rats, but it was normal in adult hypertensive animals. These results implicate adrenergic neurons in the brainstem and noradrenergic neurons in the hypothalamus in the development of spontaneous (genetic) hypertension in rats.

Animals

Serotonergic innervation of the forebrain: effect of lesions on serotonin and tryptophan hydroxylase levels.

Concentrations of serotonin and tryptophan hydroxylase activity in individual hypothalamic and limbic nuclei, as well as cortical regions, were measured by radioenzymatic microassays after dorsal raphe nucleus lesions and various surgical transections of the brain stem. Fourteen days after lesioning of the dorsal raphe nucleus there were 43-65% decreases in 5-HT concentrations of certain hypothalamic and limbic nuclei. More pronounced decreases were found in the parietal cortex and in the locus coeruleus and substantia nigra. Degenerations of nerve terminals in various regions of the hypothalamus and the limbic system were detected by electron microscopic studies 1-8 days after dorsal raphe nucleus lesions. There was no change in the 5-HT concentration of the spinal cord following dorsal raphe nucleus lesions. Surgical transections at the level of mesencephalic-pontine junction caused no significant changes in 5-HT concentrations or tryptophan hydroxylase levels in the hypothalamus, limbic system, cerebral cortex or spinal cord. Serotonergic fibers ascending from the mesencephalic raphe nuclei constitute a well circumscribed bundle dorsal to the interpeduncular nucleus. The axons enter the hypothalamus between the mammillary body and crus cerebri just ventral to the medial forebrain bundle. The ascending pathway contains all the ascending 5-HT fibers innervating the hypothalamus and the rostral limbic and cortical areas.

Animals

Phenylethanolamine: a new putative neurotransmitter in Aplysia.

Phenylethanolamine is present in the Aplysia nervous system in concentrations similar to that of octopamine. These are receptors that are very specific for phenylethanolamine, which on different neurons mediate sodium, chlorine, or potassium conductance increase responses. These observations indicate that phenylethanolamine may act as a neurotransmitter in Aplysia.

Animals

Octopamine.

Octopamine is highly concentrated in neurones of several invertebrate species. Unlike in mammals, octopaminergic neurones in invertebrates are spatially separated from catecholaminergic neurons. In identified nerve cells of Aplysia, however, this amine coexists with other putative neurotransmitters. Octopamine is synthesized in nerves from tyrosine and tyramine and metabolised mainly by monoamine oxidase. When lobster nerves are depolarized, octopamine is liberated by a Ca2+-dependent process. A specific adenylate cyclase is stimulated by octopamine in several invertebrates to activate phosphorylase in the cockroach, induce a light-flash in firefly lattern or inhibit rhythm contractions in locust muscle. All of these observations provide compelling evidence that octopamine is a neurotransmitter in invertebrates. In mammals octopamine is localised in nerves in peripheral tissues and brain where it seems to coexist with noradrenaline, the catecholamine being present in much higher concentrations. Octopamine is released from nerves together with noradrenaline and it may under certain conditions modify the actions of the adrenergic neurotransmitter. Octopamine is present in unusually high concentrations in certain neurological and hepatic diseases and may have a pathophysiological role.

Animals

Biochemical and morphologic study of catecholamine metabolism in spontaneously hypertensive rats.

Catecholamines and catecholamine-synthesizing enzymes have been studied quantitatively in specific brain areas of spontaneously (genetically) hypertensive rats by means of a combination of sensitive enzymatic-isotopic methods and a microdissecting technique. Changes in catecholamine metabolism were found to be localized to regions of the brain implicated in the regulation of blood pressure. Noradrenaline levels were decreased in specific nuclei of the anterior hypothalamus and in the nucleus interstitialis striae terminalis ventralis. The activity of the adrenaline-forming enzyme, phenyl-ethanolamine-N-methyl transferase, was increased in the A1 and A2 areas of the brain stem. These results implicate catecholamine-forming neurons in the hypothalamus and brain stem in the development of spontaneous hypertension in rats.

Animals