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Biomedical subjects

J L Montastruc

Publications and source records attributed to J L Montastruc.

At least 19 recordsLinked to original sources
PubMed1996

The discovery of vasomotor nerves.

The relative contribution of Claude Bernard and Charles Edouard Brown-Séquard to the discovery of vasomotor nerves is described and discussed. The controversy surrounding these two founding fathers of autonomic physiology and pharmacology is also summarized. In 1851, Bernard showed that section of the cervical sympathetic nerve unexpectedly elicited a marked and rapid increase in skin temperature. In 1852, Brown-Séquard extended these observations and established the relationship between blood vessels and the sympathetic nervous system. Thus, Brown-Séquard was the first to demonstrate the existence of sympathetic vasoconstrictor fibres. In contrast, Bernard discovered vasodilator nerves and is the founder of the modern concept of vasomotricity.

Anatomy↗
PubMed1996

Spectral analysis of blood pressure and heart rate, catecholamine and neuropeptide Y plasma levels in a new model of neurogenic orthostatic hypotension in dog.

The aim of the study was to compare changes in blood pressure (BP) and heart rate (HR) variability, catecholamine and neuropeptide Y (NPY) plasma levels induced by passive head-up tilt in normal and sino-aortic denervated (SAD) chloralose-anaesthetized dogs. In controls, 80 degrees head-up tilt test failed to change BP and increased HR. Plasma noradrenaline and NPY levels (but not adrenaline) significantly rose. In SAD dogs, head-up tilt test induced a marked and reproducible decrease in BP without any change in HR or noradrenaline and NPY plasma levels. In SAD dogs, spectral analysis in supine position was characterized by reduced variability in the high frequency (HF) band of the HR spectrum without changes in low frequency (LF) bands of both HR and systolic blood pressure (SBP). Head-up tilt test increased the LF component of SBP variability and decreased the HF component of HR variability in controls but failed to modify HR and BP variabilities in SAD dogs. In conclusion, sino-aortic denervation in dogs elicits a reproducible postural fall in BP with impaired adaptation of sympathetic nervous system activity. This model may be of value in evaluating the pharmacological effects of drugs for the management of orthostatic hypotension.

Adaptation, Physiological↗
PubMed1996

Ropinirole in the treatment of levodopa-induced motor fluctuations in patients with Parkinson's disease.

Forty-six patients with Parkinson's disease experiencing motor fluctuations and not optimally controlled on levodopa received as adjunct therapy a new nonergoline dopamine agonist, ropinirole, in a 3-month randomized placebo-controlled trial. Ropinirole significantly reduced the duration of off periods as assessed by self-scoring diary cards. There were more nonserious dopaminergic adverse events in the ropinirole group. More patients withdrew because of adverse events or insufficient therapeutic effect in the placebo group. Ropinirole has beneficial adjuvant effects in parkinsonian patients with moderate motor disability and motor fluctuations.

Adult↗
PubMed1995

Abnormal vestibuloocular reflex cancellation in multiple system atrophy and progressive supranuclear palsy but not in Parkinson's disease.

We have measured the gain of the vestibuloocular reflex (VOR) in darkness and its cancellation by fixation in 37 patients with Parkinson's disease (PD), 26 patients with multiple system atrophy (MSA), 11 patients with progressive supranuclear palsy (PSP), and 19 normal volunteers. The capacity to cancel the VOR by fixation (VOR cancellation) was significantly reduced in the MSA and PSP patients compared with the PD and normal subjects (p < 10(-4)). A VOR cancellation < 90% (i.e., the mean VOR cancellation of the normals--2 SD) was present in four PD patients, 23 MSA patients, and 11 PSP patients. This criteria distinguished PD and MSA with a 89% sensitivity and a 89% specificity. Our results demonstrate that the VOR cancellation is impaired in most patients with MSA and PSP but not with PD. In MSA patients, the abnormal VOR cancellation is probably not related to the nigrostriatal dopaminergic deficit and more likely reflects a cerebellar dysfunction. Impaired VOR cancellation is a clinical criteria to differentiate MSA and PSP from PD.

Age Factors↗
PubMed1995

Beta 3-adrenoceptors in the cardiovascular system.

Behind the classic beta 1 and beta 2-adrenoceptors, recent molecular and pharmacological studies have described a new receptor, called the beta 3-adrenoceptor, in various mammalian tissues (brown and white adipose tissue, digestive smooth muscle). Few authors have investigated the putative existence of the beta 3-adrenoceptor in the cardiovascular system. This paper reviews the available data. In vitro studies show that beta 3-adrenoceptor agonists (BRL 37344, CGP 12177) induce a relaxation of fragments of rat carotid artery which is not antagonized by propranolol. In dogs, these drugs elicit a decrease in blood pressure due to peripheral vasodilation and an increase in heart rate which is of baroreflex origin. The vasodilating effects are mainly observed in cutaneous and adipose tissue vessels and cannot be explained by any known transductional mechanism. Activation of this vascular beta 3-adrenoceptor requires higher doses of catecholamines than for beta 1- or beta 2-adrenoceptors. In humans, the cardiovascular effects of beta 3-adrenoceptor agonists are explained by the activation of beta 1- or beta 2 (and not beta 3-)-adrenoceptors. These studies suggest the presence of vascular (but not cardiac) beta 3-adrenoceptors in dogs. In other species, including man, the presence of such cardiac beta 3-adrenoceptors remains to be resolved. Their physiological relevance remains unknown.

Adrenergic beta-Agonists↗
PubMed1995

Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist.

Adrenoceptors are involved in the control of the activity of the autonomic nervous system and especially the sympathetic nervous system. Activation of alpha 2-adrenoceptors decreases sympathetic tone whereas their blockade has an opposite effect. However, previous investigations have shown that yohimbine (a potent alpha 2-adrenoceptor antagonist) increases salivary secretion through activation of cholinergic pathways. The aim of the present experiment was to investigate the involvement of both the sympathetic and the parasympathetic system in several pharmacological effects of yohimbine. For this purpose, salivary secretion and various endocrino-metabolic parameters (noradrenaline and insulin secretions, lipomobilization) were evaluated in conscious fasting dogs before and after blockade of either the sympathetic (with the beta-adrenoceptor antagonist agent nadolol) or the parasympathetic (with the anticholinergic agent atropine) systems. Yohimbine alone (0.4 mg.kg-1, i.v.) increased within 5-15 minutes, plasma noradrenaline (600%), insulin levels (300%), free-fatty acids (79%) and salivary secretion (143%). Atropine (0.2 mg.kg-1, i.v.) suppressed yohimbine-induced salivary secretion (90%) but did not significantly modify the yohimbine induced changes in noradrenaline (312%), insulin (277%) and free-fatty acids (102%) plasma levels. Administration of nadolol (1 mg.kg-1, i.v.) did not change the magnitude of the increase in both noradrenaline plasma levels (550%) and salivary secretion (300%) induced by yohimbine. However, nadolol totally blunted the increase in insulin (15%) and free-fatty acids (4%) plasma levels. These results show that yohimbine-induced increase in salivary secretion is a cholinergic effect whereas the increase in insulin and free fatty acids can be explained by an increase in sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1995

Central cardiovascular effects of acetylcholine in the conscious dog.

1. The effects of central cholinomimetic drugs on cardiovascular and vasoactive hormonal responses (blood pressure, heart rate, catecholamines, vasopressin, atrial natriuretic factor, neuropeptide Y plasma levels and plasma renin activity) were investigated in conscious Beagle dogs. For this purpose a catheter was chronically implanted into each dog's cisterna magna to allow repeated central injections in the awake animals. 2. Intracisternal acetylcholine (20 micrograms kg-1) significantly increased systolic and diastolic blood pressure. These changes were accompanied by an initial short term tachycardia followed by a long lasting bradycardia. Intracisternal acetylcholine also increased noradrenaline, adrenaline and vasopressin plasma levels, decreased plasma renin activity but did not modify plasma levels of neuropeptide Y and atrial natriuretic factor. 3. The effects of acetylcholine were completely abolished by pretreatment with intracisternal injection of the muscarinic antagonist, atropine (5 micrograms kg-1) but not by the intracisternal injection of the nicotinic antagonist, mecamylamine (25 micrograms kg-1). 4. The present results demonstrate that there are qualitative and quantitative differences between the central cardiovascular effects of acetylcholine in conscious dogs compared to what we previously reported, using a comparable protocol, in anaesthetized dogs. Under both conditions, we observed a central cholinergically mediated increase in blood pressure secondary to an increase in sympathetic tone and vasopressin release but these responses were shorter (less than 10 min) in the conscious dogs than in anaesthetized dogs (more than 10 min). Moreover, we detected in the response to the central cholinergic stimulation in the conscious dogs a significant increase in plasma adrenaline levels and biphasic changes in heart rate which were not described previously in the anaesthetized dog.

Acetylcholine↗
PubMed1995

Relationships between kallikrein secretion, kallikrein excretion and beta-adrenoceptors in kidney cortical slices from neurogenic hypertensive dogs.

1. Sinoaortic denervation (SAD) in dogs is characterized by an increase in blood pressure and heart rate as well as the development of renal morphological lesions similar to those observed in essential hypertension in human subjects. To assess the effect of SAD on the secretion of kallikrein kinin systems (KKS), we studied the in vitro secretion of kallikrein by renal cortical slices of normal and neurogenic hypertensive dogs (1 and 18 months after SAD). The method using renal cortical slices allowed the study of secretion of kallikrein independently of renal perfusion pressure. The number of renal beta-adrenoceptors was measured by [125I]-cyanopindolol binding. 2. SAD was associated with a marked increase in urinary kallikrein excretion at one month and a significant decrease at 18 months when compared with controls. Both changes were statistically significant (P < 0.05). Concurrently, a progressive increase in in vitro kallikrein secretion was observed (+80 +/- 10% and +179 +/- 48%, 1 and 18 months after SAD, respectively). Moreover, the cortical slices obtained from sinoaortic denervated dogs contained more kallikrein than the control cortical slices (+32 +/- 16% and +55 +/- 7%, 1 and 18 months after SAD, respectively). 3. Renal beta-adrenoceptor number significantly (P < 0.05) decreased 18 months after SAD from 18 +/- 2 to 8 +/- 3 fmol mg-1 protein without any change in affinity constant. 4. Although there was no test of association, because the number of renal beta-adrenoceptors decreased whereas kallikrein secretion increased, the present data could suggest a beta-adrenoceptor-mediated inhibition of kallikrein secretion. These results show that although the urinary kallikrein is decreased, the tissue secretory capacities are enhanced. This could suggest a renal compensatory mechanism possibly involved in tissue protection in dogs after SAD, although such a mechanism is not sufficient to reverse hypertension.

Animals↗
PubMed1995

Effects of dopaminergic drugs on the sympathoadrenal system.

Several studies have suggested that dopamine (DA) plays a major role in cardiovascular functions. Dopaminergic receptors have been found on sympathetic nerve terminals (DA2), kidney (DA1, DA2), vascular smooth muscle (DA1) as well as on sympathetic ganglia (DA1, DA2) and adrenal gland (DA1, DA2). Previous studies have shown that DA2 receptor stimulation by a specific DA2 agonist, quinpirole (1) elicits a peripheral depressor action (decreased blood pressure) and a central pressor component involving an increase in both sympathetic tone and vasopressin release and (2) does not affect under in vivo conditions adrenal catecholamine release. The present study investigates the effects of fenoldopam, a specific DA1 receptor agonist on both cardiovascular responses and catecholamine release from the adrenal medulla. In conscious normal dogs, fenoldopam (10, 20 and 40 micrograms/kg i.v.) elicited a decrease in blood pressure and a marked increase in heart rate associated with a rise in plasma catecholamine levels. The increase in heart rate is only due to baroreflex mechanism since fenoldopam (conversely to DA2 receptor agonists like quinpirole) does not exert a central excitatory component (as shown by the absence of cardiovascular effects after intracisternal injection). Moreover, in sinoaortic denervated dogs (i.e. animals deprived from baroreflex pathways), the decrease in arterial blood pressure was more important than in normal dogs. Heart rate was unchanged. In these animals, DA1 stimulation induced a decrease in sympathetic tone, as shown by the significant fall in plasma noradrenaline levels. These "in vivo" data clearly demonstrate the inhibitory role of ganglionic DA1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1995

Effects of acute levodopa administration on blood pressure and heart variability in never treated parkinsonians.

The effects of levodopa on autonomic nervous system (ANS) were investigated through the measurement of blood pressure (BP) and heart rate (HR) variability in 15 de novo parkinsonian who never received dopaminergic drugs. BP and HR were obtained using digital photoplethysmography in supine and standing positions. Measurements were achieved 90 min after administration, in a double blind cross-over way, of placebo or levodopa (200 mg)+benserazide (50 mg). Spectral analysis was performed using fast Fourier transformation (FFT) on 512 consecutive SBP and HR values. Spectral modulus was integrated for calculation of total spectra and of low frequency (LF: 66-129 mHz) or high frequency band (HF: respiratory frequency +/- 50 mHz). After placebo, orthostatism was followed by a significant increase in BP and HR whereas relative variabilities in LF and HF remained unchanged. After levodopa, BP was significantly lower in supine position without changes in HR and LF. During orthostatism, changes observed in BP and in FFT were similar to those observed during placebo period. These data indicate that levodopa reduces supine and standing BP but does not impair orthostatic adaptation. This effect is not due to modification of BP or HR variability and appears to independent of any direct effect on ANS.

Blood Pressure↗
PubMed1995

Involvement of renal dopaminergic system in experimental neurogenic arterial hypertension.

The effect of chronic salt loading (10 g of NaCl for a period of 7 days) on urinary dopamine release has been investigated in 3 groups of beagle dogs: normotensive dogs (group 1: n = 7), and 2 groups of dogs made hypertensive by chronic sinoaortic denervation [group 2: (n = 6) during the first 4 months after sinoaortic denervation i.e. a model of arterial hypertension with high levels of plasma catecholamines and group 3: (n = 6) one year after denervation i.e. a model of arterial hypertension with normal sympathetic tone]. In normal dogs (group 1), salt loading induced an increase in urinary dopamine excretion during the two first days after salt loading. The rise in urinary dopamine was blunted in group 2. It was not observed in group 3. Salt loading failed to change arterial pressure and heart rate in the three groups of animals. These data show an alteration of the renal dopaminergic system in hypertensive sinoaortic denervated dogs suggesting that a dopaminergic impairment can appear during the development of arterial neurogenic hypertension.

Animals↗
PubMed1995

Antivertigo medications and drug-induced vertigo. A pharmacological review.

The approach to drug treatment of vertigo is almost exclusively symptomatic. There are 3 major goals for drug treatment of vertigo. The first one is to eliminate the hallucination of motion. Drugs with vestibular 'suppressant' properties are used for this purpose. The major vestibular suppressants are anticholinergic and antihistamine drugs. The second goal is to reduce the accompanying neurovegetative and psychoaffective signs (nausea, vomiting, anxiety). Antidopaminergics are used for this purpose. The third goal is to enhance the process of 'vestibular compensation' to allow the brain to find a new sensory equilibrium in spite of the vestibular lesion. Until now, the pharmacological manipulation of vestibular compensation has been assessed in animals but not in humans with vestibular lesions. Vestibular suppressant drugs delay rather than enhance compensation. A variety of other drugs is also used in the treatment of vertigo, including benzodiazepines, histaminergic agents, sympathomimetics and calcium antagonists. Their mechanism of action is poorly understood. The data base derived from clinical trials evaluating antivertigo medications is often questionable because of methodological limitations. This explains why habits of prescription are mainly empirical, and why striking differences can be noticed from one country to another. We can hope that new treatments may emerge from the present interest in receptor subclasses and neuromodulators of the vestibular system, and we must be ready to evaluate these potential new pharmacological agents with reliable clinical methods in humans.

Animals↗