[History of clinical pharmacology in France: adaptation, evaluation, defense and illustration of drug in France 1978-1981].

This text illustrates some unknown aspects of the history and beginnings of clinical pharmacology in France in the late 1970s and early 1980s From the current situation, development and objectives of clinical pharmacology are recalled as well as obstacles necessary to overcome to change the paradigm in the field of drug evaluation and appropriate use in France. The text recalls this important moment where French medicine and medical pharmacology entered the modern era.

Characterization of the central muscarinic cholinoceptors involved in the cholinergic pressor response in anesthetized dogs.

Previous reports have shown that an intracisternal (i.c.) injection of acetylcholine in the dog increases both arterial blood pressure and plasma levels of noradrenaline and vasopressin via central muscarinic receptors.

Effect of losartan on afferent nerve stimulation.

The present study was undertaken to investigate the effects of losartan, a non-peptide angiotensin II subtype 1 (AT1) receptor antagonist, on both the pressor responses elicited by stimulation of afferent vagal nociceptive fibres and the involvement of the sympathetic nervous system (evaluated by plasma levels of noradrenaline and its co-neurotransmitter neuropeptide Y) in dogs. Electrical stimulation of the afferent fibres of the vagus (1, 5, 10 and 20 Hz) elicited a frequency-dependent increase in blood pressure and heart rate. Plasma noradrenaline levels only increased after stimulation at frequencies of 10 and 20 Hz.

Lack of haemodynamic effects of nitric oxide on post-capillary pulmonary hypertension induced by acute sino-aortic denervation.

1. The aims of the present experiments were to define a new experimental model of pulmonary hypertension induced by a post-capillary mechanism and to assess the haemodynamic effects of nitric oxide on post-capillary pulmonary hypertension. 2.

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.

A study of tolerance to apomorphine.

1. The present study was designed to investigate tolerance to several pharmacological effects of apomorphine. 2.

Effects of pentobarbital and etomidate on plasma catecholamine levels and spectral analysis of blood pressure and heart rate in dogs.

The present paper investigates the effects of two anaesthetic drugs (pentobarbital and etomidate) on both short-term variabilities of systolic blood pressure (SBP) and heart rate (HR) using fast Fourier transformation and catecholamine plasma levels. HR and BP were continuously recorded through an arterial catheter and blood samples were taken from the jugular vein. Spectral analysis was performed first in the conscious state and six minutes after induction of anaesthesia on a series of 256 consecutive BP and HR values (delta t: 2 Hz).

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.

[Adverse drug effect notifications by nurses and comparison with cases reported by physicians].

The aim of the present study was to investigate the characteristics of adverse drug reactions reported by hospital doctors and nurses from Toulouse University Hospital between 1992 and 1993. During these two years, doctors and nurses reported 1498 and 164 adverse drug reactions respectively. Nurses reported significantly more cutaneous side effects than doctors (50 vs 24 per cent).

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).

[Absence of the effect of nitric oxide on pulmonary and systemic hypertension induced by sino-aortic denervation].

Inhaled nitric oxide, a selective pulmonary vasodilator, reverses hypoxic pulmonary vasoconstriction and is an effective treatment in some cases of human pulmonary hypertension. Localization of nitric oxide synthase had indicated a neural role for nitric oxide. Thus, we studied the interactions between inhaled nitric oxide and systemic and pulmonary vascular reactivity in acute neurogenic hypertension.

Naloxone does not prevent apomorphine-induced emesis or hypotension in dogs.

Previous data have shown that apomorphine-induced respiratory depression can be reversed by the opiate antagonist, naloxone. The present study investigates the influence of naloxone on cardiovascular changes and vomiting elicited by apomorphine in dogs. In chloralose-anaesthetized animals, naloxone (0.

Effects of insulin on the release of neuropeptide Y, [Met5]enkephalin and catecholamines from dog adrenal medulla.

Insulin-induced hypoglycaemia is a well-known stimulating factor for the release of adrenaline from adrenal medulla. The present experiment investigates the co-release of catecholamines and neuropeptides (neuropeptide Y and [Met5]enkephalin) from the adrenal medulla in chloralose-anaesthetized dogs after intravenous administration of insulin (0.3 U/kg).

[Physiological mechanisms of cardiovascular adaptation to orthostatism. Role of the sympathetic nervous system and pharmacological implications].

The main physiological adaptative systems occurring during orthostatism are discussed. The nervous mechanisms and especially baroreceptor pathways allow a rapid adaptation to the new hemodynamic conditions whereas hormones (mainly vasopressin) are involved later. The role of baroreflex and cardiocirculatory mechanisms is explained by the description of adaptative mechanisms in giraffe, an animal with its brain so far above the ground.

Effects of clonidine, dihydralazine and splanchnic nerve stimulation on the release of neuropeptide Y, MET-enkephalin and catecholamines from dog adrenal medulla.

Various neuropeptides are costored together with catecholamines in the adrenal medulla. The concurrent release (evaluated by adrenal vein plasma levels) of these neuropeptides [neuropeptide Y (NPY), met-enkephaline (ME)] and catecholamines [adrenaline (A) and noradrenaline (NA)] from the adrenal gland was examined in chloralose-anesthetized dogs after intravenous administration of clonidine (10 micrograms/kg) and dihydralazine (1 mg/kg). These results were compared to those obtained after the stimulation of the right splanchnic nerve at 1, 5 and 10 Hz frequencies.

[Mechanism of receptor regulation during repeated administration of drugs].

The effects of drugs is mainly explained by their action on specific receptors located on target cells. However, the receptors are can be regulated by changes into the levels of the physiological neurotransmitter and/or by drugs. A chronic treatment by an agonist induces a desensitization leading to a decrease in cellular response.

[Co-release of neuropeptides and catecholamines by adrenal medulla].

Different neuropeptides are costored together with catecholamines in the adrenal medulla. The concurrent release of these neuropeptides [neuropeptide Y (NPY), met-enkephalin (ME)] and catecholamines (adrenaline and noradrenaline) from the adrenal gland was examined in chloralose-anesthetized dogs after intravenous administration of dihydralazine (1 mg/kg) and insulin (0.3 U/kg).

Renal morphological changes after sinoaortic denervation in dogs.

The present study investigates morphological renal lesions in sinoaortic-denervated dogs 1 (n = 6) and 18 (n = 5) months after sinoaortic denervation compared with sham-operated controls (n = 8). After 1 month, a marked hyalinization and moderate thickening of the media of arterioles and small interlobular arteries were observed. These changes associated with edema and intimal thickening led to a narrowing of the lumen.

The effect of yohimbine on sympathetic responsiveness in essential hypertension.

We have studied the sympathetic response to blockade of presynaptic alpha 2-adrenoceptors in essential hypertension by measuring plasma concentrations of noradrenaline after a single oral dose of yohimbine, an alpha 2-adrenoceptor antagonist. Mean baseline plasma noradrenaline and adrenaline concentrations were similar in the hypertensive and normotensive groups. Yohimbine (0.

A study of alpha 1- and alpha 2-adrenoceptor responsiveness in diabetic insipidus dogs.

The present study was performed to investigate the participation of circulating vasopressin in alpha-adrenoceptor responsiveness. Thus, we compared the pressor responses induced by selective alpha 1-or alpha 2-adrenoceptor stimulation in two groups of conscious dogs: a) normal animals and b) animals with surgically-induced diabetes insipidus. In addition, platelet alpha 2-adrenoceptors labelled with (3H)RX821002 were compared in the two groups.

Effect of oxodipine, a novel dihydropyridine calcium channel blocker, in neurogenic hypertensive dogs.

The effects of an acute intravenous injection of oxodipine (5, 20 and 50 micrograms/kg), a new dihydropyridine calcium channel blocker, on blood pressure and heart rate were investigated in arterial neurogenic hypertension elicited in anesthetized dogs by acute sinoaortic denervation. This model is associated with disruption of baroreflex pathways and heart denervation, allowing a direct investigation of the effects of the drug on heart rate and blood vessels. The low dose (5 micrograms/kg) of oxodipine remained ineffective, whereas doses of 20 and 50 micrograms/kg of oxodipine elicited a decrease in blood pressure with no change in heart rate.

Naloxone or haloperidol but not yohimbine reverse apomorphine-induced respiratory depression.

Intravenous injection of low doses of naloxone was found to reverse the respiratory depression induced by apomorphine in chloralose-anesthesized dogs. Similar results were obtained with haloperidol, whereas yohimbine remained ineffective. These data suggest that apomorphine depresses respiratory rate through a mechanism involving both dopamine and opiate mechanisms but not alpha 2-adrenoceptors.