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Biomedical subjects

R Pagliari

Publications and source records attributed to R Pagliari.

8 recordsLinked to original sources

Physical conditioning in rats influences the central and peripheral catecholamine responses to sustained exercise.

We have investigated the effect of treadmill running in rats (25m.min-1 using a 3% gradient; for 1 h or 2 h) on the cortical extracellular concentrations of noradrenaline (NA) and its main metabolites-3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol- and the plasma adrenaline (A) and NA concentrations in relation to prior physical conditioning (1 or 2-h running.day-1 for 12 days). Cortical microdialysates and peripheral blood were collected during 1-h resting, 1-h or 2-h running and for 1 h after exercise. Catecholamines and their metabolites were quantitated using high performance liquid chromatography with electrochemical detection. Treadmill running stimulated concomitantly peripheral catecholamine secretion and central noradrenergic activity, i.e. NA turnover and release. The effect extended into the recovery period even more as the duration of the run increased. Prior physical conditioning greatly influenced the central and peripheral catecholamine responses: the 1-h trained rats experienced the 2-h run as a stressful new event eliciting great long-lasting catecholamine responses, whereas the 2-h trained rats exhibited a progressive sustained catecholamine increase with an earlier onset of the central NA release. The data are discussed in relation to the psychological and intellectual effects of exercise and physical fitness in humans. In addition, the positive correlation found between the central noradrenergic activation and peripheral A secretion confirmed and extended our previous observations in exercising men and gave support to the hypothesis that the elevation of circulating A can be a relevant factor mediating--directly or indirectly--the exercise-induced central effects.

Animals↗

Differential regional and kinetics effects of piribedil and bromocriptine on dopamine metabolites: a brain microdialysis study in freely moving rats.

Brain microdialysis coupled to HPLC was applied to freely moving rats to investigate the regional kinetics of piribedil and bromocriptine on the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in striatum, nucleus accumbens, and frontal cortex. Both D2 agonists (20 mg/kg i.p.) decreased DOPAC and HVA in the three brain regions. The responsiveness of frontal cortex to both compounds was greater than those previously reported with other dopaminergic drugs. Regional and temporal differences were observed under piribedil: DOPAC and HVA levels decreased more in the nucleus accumbens than in striatum or frontal cortex but increased over basal values from the 5th hour in the frontal cortex suggesting a late stimulatory effect of piribedil on dopamine synthesis in this area. Such regional effects differentiate piribedil from most other D2 agonists and could explain some behavioural and therapeutic actions possibly related to involvement of nucleus accumbens or/and frontal cortex.

3,4-Dihydroxyphenylacetic Acid↗

Norepinephrine release in the rat frontal cortex under treadmill exercise: a study with microdialysis.

Cortical norepinephrine (NE) release and metabolism were studied by using chronic microdialysis in rats performing a treadmill exercise at 25 m/min with a 3% slope. Cortical microdialysates and peripheral blood were collected at rest, during 1- or 2-h treadmill running, and for 1 h after exercise. Microdialysate NE and its main metabolites, 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol, and plasma epinephrine (Epi) and NE were determined by high-performance liquid chromatography with electrochemical detection. The results show that treadmill running is able to stimulate concomitantly peripheral catecholamine secretion and central noradrenergic activity, i.e., NE turnover and release. The duration of the central activation and its prolongation over recovery period increases as the duration of the running increases. A positive correlation was found between the central noradrenergic activation and peripheral Epi secretion but not peripheral NE. These findings confirm and extend our previous observations in exercising men and give support to the hypothesis that the elevation of circulating Epi can be a relevant factor mediating, directly or indirectly, the exercise-induced central neurochemical, psychological, and cognitive changes.

Animals↗

[Plasma methoxyamines assay: a practical advance for the diagnosis of pheochromocytoma].

Measurement of plasma methoxyamines is aimed to provide a reliable plasma marker readily available for any patient suspected of having a pheochromocytoma. The present HPLC method is able to detect methoxyamine amounts as low as 0.2 nmoles/l and allows the determination of both free or conjugated methoxyamines (metanephrine MN and normetanephrine NMN) in normal subjects, treated or untreated patients and a fortiori in pheochromocytoma. The analytical specificity is excellent. Among most usual antihypertensive drugs, only conversion enzyme inhibitors and diuretics induce in some patients a moderate increase of NMN with minor consequence in values interpretation. The kidney plays a major role in the blood clearance of methoxyamines and any alteration of renal function is associated to the increase of plasma methoxyamine levels. Plasma methoxyamines have a long half-life and are long-lasting integrated markers of catecholamine secretion; at variance with plasma free catecholamines, they are able to afford the presence of a secreting pheochromocytoma whatever the clinical presentation--asymptomatic or paroxysmal form between the crisis. The diagnostic sensitivity (at least 98%) is equal to that of urinary methoxyamines, far higher than plasma or urine catecholamines or urine VMA (60 to 70%).

Adrenal Gland Neoplasms↗

Determination of free and conjugated normetanephrine and metanephrine in human plasma by high-performance liquid chromatography with electrochemical detection.

A simple method for the simultaneous assay of normetanephrine and metanephrine (both free and conjugated) in human plasma by high-performance liquid chromatography with electrochemical detection has been developed. The hydrolysed plasma is purified on a Dowex 50 H+ column, and the methoxylated amines are eluted with ammonia-methanol. The methoxyamines are assayed using a dual-series electrode arrangement with differential current measurement. This system greatly improves the assay specificity toward endogenous or exogenous metabolites and drugs. The high sensitivity of the method enables the determination in normal subjects of levels of normetanephrine and metanephrine.

Chromatography, High Pressure Liquid↗

Measurement of plasma methoxyamines for the diagnosis of pheochromocytoma.

Urinary methoxyamine determination is considered as the most sensitive and specific parameter for the diagnosis of pheochromocytoma. Since blood sampling is easier to perform, we developed a new HPLC method to assay metanephrine (MN) and normetanephrine (NMN) in plasma. We now report the results for total (free and conjugated) MN and NMN in 22 cases of pheochromocytoma compared to 26 healthy subjects, 33 patients with essential hypertension, 14 with miscellaneous diseases and 4 patients with renal failure. The mean normal values (mean +/- SD) were 0.40 +/- 0.10 ng/ml for MN and 0.85 +/- 0.25 ng/ml for NMN. The sum of MN+NMN was 1.25 +/- 0.28 and the range 0.9-1.9. In essential hypertension, the range of NMN+MN was 1.2-6.0. In the 4 renal failures, both MN and NMN were drastically increased. In 49 samples drawn from 22 pheochromocytomas, MN was elevated over the hypertensive range in 34 samples and NMN in 47 samples. The total MN+NMN ranged from 6.2 to 436 ng/ml; this figure was observed whatever the clinical presentation even in silent tumors or in paroxysmal forms between the crisis. After tumor removal, the values dropped rapidly. In conclusion, plasma determination of MN and NMN provides a highly sensitive and specific biological pointer for the diagnosis of pheochromocytoma in patients without renal failure.

Adrenal Gland Neoplasms↗

Effect of almitrine administration on pulmonary arterial pressure in resting and exercising dogs.

In addition to its well-known ventilatory effect, a small rise in pulmonary arterial pressure or pulmonary vascular resistance is occasionally observed with chronic administration of almitrine. In order to test the hypothesis of enhancement of exercise pulmonary vasoconstriction by almitrine, mongrel dogs were studied at rest and during submaximal exercise before and after 4 weeks of chronic ingestion of almitrine (10 mg/kg). It was shown that resting pulmonary arterial pressure (PAP) remained unchanged by almitrine treatment. However, when exercise was superimposed on almitrine medication, PAP was significantly increased throughout the exercise bout. Thus, the rise in PAP during the 20th min of exercise averaged 8.7 +/- 3.4 mm Hg after almitrine treatment while PAP increased by only 1.3 +/- 1.7 mm Hg before medication. The exaggerated exercise-induced PAP response in conjunction with the enhanced secretion of norepinephrine that we observed during almitrine treatment suggests that catecholamine could be involved in the pulmonary haemodynamic adjustments. Furthermore, mixed-venous PO2 (PvO2) both during rest and exercise declined with the prolongation of almitrine ingestion, suggesting that PvO2 might possibly be implicated in the pulmonary haemodynamic response to almitrine, in the same way as it is involved in the hypoxia-induced pulmonary vasoconstriction. These findings demonstrate that almitrine medication, even at a high dose, does not have any deleterious effect on pulmonary vasculature in resting conditions, but prolonged submaximal exercise should be proscribed in patients on a long-term therapy.

Almitrine↗