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Biomedical subjects

G Pistritto

Publications and source records attributed to G Pistritto.

29 records · Page 2Linked to original sources

A discrepancy between platelet alpha 2-receptor density and functional circulatory changes in hypertensives.

To investigate whether differences exist in peripheral alpha 2-adrenoceptors between normotensive and hypertensive subjects, we determined platelet alpha 2-adrenoceptor density in 10 (7 males) untreated essential hypertensives (mean age of 51.1 years, range of 44-59 years) and in 10 age- and sex-matched normotensive controls. Moreover, in hypertensive patients, we examined the relationship between receptor density and cardiovascular reactivity to mental arithmetic, static handgrip, and bicycle exercise, to verify the hypothesis that alpha 2-adrenoceptors might play a role in modulation of hemodynamic response to sympathetic stimuli. alpha 2-Adrenoceptor density, as calculated by binding of [3H]yohimbine to platelets, was significantly higher in essential hypertensives (314.8 +/- 38.7 fmol/mg) than in normotensive subjects (213.6 +/- 34.7 fmol/mg) (p less than 0.05), whereas receptor affinity was similar in both groups (4.0 +/- 0.5 nM hypertensives, 4.3 +/- 0.5 nM normotensives; p greater than 0.05). Mental arithmetic increased mean arterial pressure (MAP) by 21.5% from basal values and heart rate (HR) by 13.2%. During isometric exercise, MAP increased by 38.1% and HR by 24.7%, while during bicycle ergometry, mean increases in MAP and HR from baseline were of 27.2 and 54.3%, respectively. No correlation was found between platelet alpha 2-adrenoceptor density and percent changes in MAP induced by all tests, or between adrenoceptors and absolute basal and peak MAP values. Our findings suggest that in hypertensive patients, peripheral alpha 2-adrenoceptors are increased with respect to matched normotensives, but these receptors seem not to be involved in the modulation of cardiovascular adaptation to enhanced sympathetic activity.

Adult↗

Neuropeptide Y increases the inhibitory effects of clonidine on potassium evoked 3H-noradrenaline but not 3H-5-hydroxytryptamine release from synaptosomes of the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat.

The release of 3H-noradrenaline (3H-NA) and of 3H-5-hydroxytryptamine (3H-5-HT) evoked by high-K+ (15 mM) was studied in synaptosomes isolated from the hypothalamus and the frontoparietal cortex of the male Sprague-Dawley rat using a superfusion apparatus. Based on concentration-response curves obtained by analyzing the full-time course of the inhibitory effects of clonidine on 3H-NA and on 3H-5-HT release neuropeptide Y (NPY) (1 nM) was shown to significantly increase the ability of clonidine to inhibit 3H-NA release in synaptosomes isolated from the hypothalamus and from the frontoparietal cortex. NPY (1 nM) alone had no effect on K+-evoked 3H-NA release from these regions. In contrast, NPY (1 nM) did not modulate the inhibitory effects of clonidine on 3H-5-HT release in the above mentioned regions. These results indicate that NPY can increase the sensitivity of the alpha 2-autoreceptors belonging to hypothalamic NA and/or to adrenaline nerve terminals and to cortical NA nerve terminals, while the alpha 2-heteroreceptors inhibiting 3H-HT release in the same brain regions appear not to be regulated by high affinity NPY receptors. Thus, alpha 2-autoreceptors and alpha 2-heteroreceptors appear to be differentially controlled by high affinity NPY receptors at least with regard to regulation of 3H-NA and 3H-5-HT release, respectively.

Animals↗

Different regulation of serotonin receptors following adrenal hormone imbalance in the rat hippocampus and hypothalamus.

Adrenal influence on serotonin (5-HT) transmission in the hippocampal and hypothalamic areas was studied in adrenalectomized rats receiving or not corticosterone replacement. After adrenalectomy, the 5-HT presynaptic receptors were desensitized both in hippocampus and hypothalamus: a significant increase in 5-HT 1 and 5-HT 2 receptor binding numbers took place in membranes from the hippocampus, but not in hypothalamus, while no changes in affinity of receptors to radioligands were observed in either brain area. Corticosterone treatment restored the adrenalectomy-impaired 5-HT autoreceptor sensitivity in hippocampus and hypothalamus and 5-HT density receptor sites in the hippocampus. Serotonin autoreceptor down-regulation following adrenalectomy may increase 5-HT release to maintain the constancy of serotonergic transmission in the brain and 5-HT modulated CRH-ACTH release to compensate the plasma corticosteroid drop. Corticosterone seems to display a distinct tonic control on serotonin transmission in both hippocampus and hypothalamus, the diversity being due to the different roles played by the hormone in these brain regions.

Adrenalectomy↗

Reduced inhibitory effects of clonidine and neuropeptide Y on 3H-noradrenaline release from synaptosomes of the medulla oblongata of the spontaneously hypertensive rat.

The release of 3H-noradrenaline (3H-NA) evoked by high-K+ (15 mM) was studied in synaptosomes isolated from the medulla oblongata of the normotensive Wistar-Kyoto and spontaneously hypertensive male rat (14 weeks old) using a superfusion apparatus. Based on concentration-response curves clonidine was shown to have a reduced ability to inhibit 3H-NA release in synaptosomes isolated from the spontaneously hypertensive rat (SHR) versus the normotensive rat. Furthermore, only a high concentration of NPY (100 nM) had the ability to enhance the inhibitory effects of clonidine on 3H-NA release in synaptosomes isolated from the medulla oblongata of the SH male rat, while 1 nM of NPY was effective in synaptosomes isolated from the medulla oblongata of the normotensive Wistar-Kyoto rat. These results may indicate a reduced presynaptic alpha 2-adrenoceptor and NPY receptor function to inhibit 3H-NA release from NA and/or adrenaline (A) nerve terminals in the medulla oblongata of the adult 14 weeks old SHR.

Animals↗

Prolactin-lowering ability of (+/-)-idazoxan may be linked to a central noradrenergic-serotonergic interplay.

2-[2-(1,4-benzodioxanyl)-2-imidazoline] (idazoxan) sometimes lowers basal prolactin levels in the male adult rat, but strongly inhibits hyperprolactinemia in suckling rats. A possible antido paminergic drug effect is not involved, due to its inability to modify prolactin release from superfused pituitary in vitro as well as rat haloperidol hyperprolactinemia in vivo. On the contrary, in the rat idazoxan counteracts hyperprolactinemias due to central presynaptic serotonergic neurotransmission increase (5-hydroxytryptophan, D-fenfluramine and fluoxetine) but not those related to direct agonists at 5-hydroxytryptamine (5-HT) receptor (6-chloro-2-[1-piperazinyl] pyrazine, MK 212; 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane, DOI). (+/-)-Idazoxan does not modify [3H]-5-HT release from isolated hypothalamic synaptosomes. It displays an affinity for alpha-2 adrenergic autoreceptors about 250-fold more than for alpha-2 heteroreceptors located on 5-HT nerve terminals in the central nervous system (pA2 value 9.99, equivalent to a Kb of 0.1 nM vs. pA2 7.60 equivalent to a Kb of 2.5 nM). The noradrenergic outflow selectively induced by idazoxan in the brain may negatively modulate the 5-HT release from the relevant nerve endings, thus preventing prolactin release due to an activation of presynaptic serotonergic axons induced both physiologically (lactation) and pharmacologically (5-hydroxytryptophan, D-fenfluramine and fluoxetine) without influencing hyperprolactinemias related to a direct activation of serotonergic receptors (MK 212 and DOI). Other blocking agents, strong but less selective than (+/-)-idazoxan for noradrenergic brain neurotransmission, do not modify or increase blood prolactin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Alpha 2-adrenoceptor blocking properties of idazoxan stereoisomers: stereoselectivity for presynaptic alpha 2-adrenoceptors.

The alpha 2-adrenoceptor blocking properties of idazoxan enantiomers were evaluated at pre- and postsynaptic level. The antagonism of the two idazoxan stereoisomers was assessed, at presynaptic level, by their ability to antagonize clonidine at the alpha 2-adrenoceptors regulating noradrenaline release. The antagonist (+)-idazoxan showed an affinity towards the alpha 2-autoreceptors 40 times higher than that showed by (-)-idazoxan. Binding studies revealed (+)-idazoxan to be 7-8 times more potent than (-)-idazoxan in inhibiting the p-[3H]aminoclonidine binding. These results indicate a different affinity of alpha 2-adrenoceptors for the two idazoxan stereoisomers, thus suggesting that the alpha 2-adrenoceptors located pre- and postsynaptically may be of two stereochemically different subtypes.

Animals↗

Neuropeptide Y enhances the inhibitory effects of clonidine on 3H-noradrenaline release in synaptosomes isolated from the medulla oblongata of the male rat.

In studies on superfused synaptosomes from the rat medulla oblongata, the inhibitory effects of the alpha 2-adrenergic agonist clonidine (0.1 microM) on potassium (15 mM K+) induced 3H-noradrenaline (NA) release was potentiated by 20%, when neuropeptide Y was added to the system. The effect of NPY was detectable at low concentrations (1 nM) and was not dose-dependent. Neuropeptide Y alone produced no significant effects on 3H-NA release. The results may indicate the existence of a presynaptic NPY receptor on the noradrenaline and/or adrenaline nerve terminals, which may enhance the presynaptic alpha 2-adrenoreceptor function to inhibit 3H-NA release.

Animals↗

Ear lobe bilateral necrosis by levamisole-induced occlusive vasculitis in a pediatric patient.

We describe a bullous-hemorrhagic reaction of the ear lobes in a child with nephrosis after levamisole intake. This drug is used in children as an alternative treatment of corticosteroid-responsive nephrotic syndrome. Histologic evaluation of a lesion revealed necrotizing vasculitis involving mainly the large vessels of the deep plexus. The lesions disappeared 25 days after discontinuation of treatment.

Adjuvants, Immunologic↗