Biomedical subjects

M A Tran

Publications and source records attributed to M A Tran.

At least 73 records · Page 4Linked to original sources

PubMed1990

Reserpine induces vascular alpha 2-adrenergic supersensitivity and platelet alpha 2-adrenoceptor up-regulation in dog.

1. The aim of the present study was to investigate the influence of catecholamine levels on the regulation of alpha 2-adrenoceptor sensitivity in dogs. 2. Blood pressure and heart rate values at rest, plasma catecholamine levels, platelet and adipocyte alpha 2-adrenoceptors as well as the alpha 2-mediated cardiovascular responses to clonidine (10 micrograms kg-1 i.v., after alpha 1-, beta-adrenoceptor plus muscarinic blockade) or noradrenaline (0.5, 1, 2 and 4 micrograms kg-1 i.v. after alpha 1- and beta-adrenoceptor blockade) were measured before and after reserpine treatment (0.1 mg kg-1 day-1 s.c. over 15 days). 3. Reserpine induced a significant decrease in resting systolic and diastolic blood pressures (213 +/- 2/87 +/- 6 mmHg before vs 158 +/- 5/59 +/- 3 mmHg after treatment) as well as in heart rate (91 +/- 2 beats min-1 before vs 76 +/- 3 beats min-1 after treatment). 4. A 5 min tilt test performed under chloralose anesthesia, failed to modify blood pressure before treatment whereas it induced a significant fall in the same animals after the 15 day treatment. Plasma levels of noradrenaline significantly decreased (262 +/- 58 vs 66 +/- 31 pg ml-1) whereas plasma adrenaline levels were unchanged. 5. The alpha 2-mediated pressor responses to noradrenaline were significantly increased after reserpine. Clonidine induced a marked pressor effect (+72 and +45% in systolic and diastolic blood pressures respectively) after reserpine treatment. This effect was suppressed by administration of RX-821002, a new specific alpha 2-adrenoceptor antagonist. 6. Reserpine treatment significantly increased platelet alpha 2-adrenoceptor number (identified with [3H]- yohimbine or [3H]-RX821002) with no change in Kd values. alpha 2-Adrenoceptor number remained unchanged in adipocytes (identified with [3H]-RX821002). 7. These results show that a 15 day treatment with reserpine induces a vascular alpha 2-adrenergic supersensitivity and an up-regulation in platelet alpha 2-adrenoceptors. In contrast, this phenomenon does not involve all the tissues since adipocyte alpha 2-adrenoceptors escape the effect of reserpine. We suggest that the levels of plasma noradrenaline play an important role in the regulation of the platelet and vascular alpha 2-adrenoceptors. In contrast, adipocyte alpha 2-adrenoceptors are not affected by changes in plasma noradrenaline levels.

Adipose Tissue↗

PubMed1990

Cardiovascular effects of central injection of acetylcholine in anaesthetized dogs: a role for vasopressin release.

1. The effect of an intracisternal injection of 20 micrograms kg-1 of acetylcholine was studied on systolic and diastolic blood pressures, heart rate, and plasma levels of noradrenaline, adrenaline, vasopressin, plasma renin activity and atrial natriuretic factor in chloralose-anaesthetized dogs, 8 of which were normal and 7 with diabetes insipidus (deprived of vasopressin secretion by surgical lesion of the hypothalamoneurohypophysial system). 2. Acetylcholine significantly increased systolic and diastolic blood pressures in both groups of animals. However, the rise in blood pressure was significantly shorter lived in the dogs with diabetes insipidus. 3. Acetylcholine significantly increased plasma levels of noradrenaline but not adrenaline in control animals and in dogs with diabetes insipidus. Noradrenaline and adrenaline responses after acetylcholine were not different in the two groups of animals. 4. Acetylcholine induced a significant increase in vasopressin plasma levels only in control animals while in dogs with diabetes insipidus vasopressin remained at nearly undetectable levels. 5. Acetylcholine significantly increased atrial natriuretic factor plasma levels only in control dogs. 6. Although plasma renin activity increased in both groups of animals after the i.c. injection of acetylcholine, this change was not significant in any group. 7. These results suggest that, in the anaesthetized dog, the central injection of acetylcholine induces a rise in blood pressure through both an increase in sympathetic outflow and a release of vasopressin.

Acetylcholine↗

PubMed1990

Decreased high affinity state in platelet alpha 2-adrenoceptors from diabetic patients with orthostatic hypotension.

Plasma catecholamine levels, total platelet alpha 2-adrenoceptor number and affinity state (using [3H]yohimbine binding) were investigated in insulin-dependent diabetic patients with (n = 12) or without (n = 10) orthostatic hypotension due to autonomic neuropathy as well as in normal control subjects (n = 6). Mean resting basal catecholamine values were similar in the three groups. One-minute standing elicited an increase in norepinephrine plasma level (but not in epinephrine plasma levels) in control group but not in diabetic patients (with or without orthostatic hypotension). The maximal number of platelet alpha 2-adrenoceptors (and KD) calculated by [3H]yohimbine saturation experiments was similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in high affinity state (inhibition experiments of [3H]yohimbine by UK14,304, a specific alpha 2-adrenergic full agonist) was significantly lower in diabetic patients with orthostatic hypotension (29.2 +/- 5.3%) than in the other two groups. No significant difference was found between the control group (60.0 +/- 2.0%) and diabetic patients without orthostatic hypotension (64.3 +/- 3.1%). Since platelet alpha 2-adrenoceptors are thought to be a suitable index of vascular alpha-adrenoceptors, the decrease in platelet alpha 2-adrenoceptors in high affinity state could explain the occurrence of orthostatic hypotension in insulin-dependent diabetic patients. Multiple pathophysiological mechanisms underly orthostatic hypotension in insulin-dependent diabetic patients and include anomalies both in the sympathetic nervous system and in alpha 2-adrenoceptor coupling.

Adrenergic alpha-Agonists↗

PubMed1990

Blood pressure and plasma catecholamines in never-treated parkinsonian patients: effect of a selective D1 agonist (CY 208-243).

We found blood pressure (BP), heart rate (HR), plasma norepinephrine (NE), and epinephrine (E) levels in the lying and the standing positions to be similar in never-treated parkinsonian patients (stages 1 and 2) and age-matched controls. CY 208-243, a new centrally active D1 agonist, significantly decreased BP, HR, and NE (but not E) values in the lying position; it elicited orthostatic hypotension and blunted the rise in NE elicited by standing up. These results indicate that the early stages of Parkinson's disease are not accompanied by major changes in autonomic cardiovascular function and suggest the involvement of central D1-receptors in the control of sympathetic tone.

Antiparkinson Agents↗

PubMed1990

Effect of quinpirole, a specific dopamine DA2 receptor agonist on the sympathoadrenal system in dogs.

The effects of quinpirole, a specific dopamine DA2 receptor agonist, were investigated on both cardiovascular responses in conscious dogs and catecholamine release from the adrenal medulla in anesthetized dogs. In conscious normal dogs, i.v. quinpirole (30 micrograms/kg) 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 due to both baroreflex and central mechanisms because a slight but significant positive chronotropic effect persists in sinoaortic denervated dogs (i.e., animals deprived of baroreflex pathways). The central origin of this excitatory effect was confirmed by two subsequent protocols: intracisterna magna injection of quinpirole (5 micrograms/kg) increased blood pressure, heart rate and plasma catecholamines; i.v. domperidone reversed the hypotensive effect of i.v. quinpirole into a pressor response. The rise in plasma catecholamines was associated with an increase in plasma vasopressin levels. In anesthetized dogs, i.v. quinpirole (10 micrograms/kg/min during 12 min), which also decreased blood pressure, failed to modify epinephrine (and norepinephrine) release from the adrenal medulla whatever the stimulation frequencies (1, 3 and 5 Hz) of the sectioned splanchnic nerve. Similar results were obtained with apomorphine (5 micrograms/kg/min during 12 min). These results show that two mechanisms are involved in the action of quinpirole: first, a peripheral depressor action (which elicits the decrease in blood pressure) and secondly, a central pressor component involving an increase in both sympathetic tone and vasopressin release. They also demonstrate clearly that peripheral DA2 receptors are not involved in the control of catecholamine release from the adrenal medulla under in vivo conditions.

Adrenal Medulla↗

PubMed1990

[Platelet alpha 2 adrenergic receptors, plasma catecholamines and orthostatic hypotension in insulin-dependent diabetic patients].

Plasma catecholamine levels, total platelet alpha 2-adrenoceptor number and affinity state (using [3H]-yohimbine binding) have been investigated in insulin-dependent diabetic patients with (n = 12) or without (n = 10) orthostatic hypotension as well as in normal control subjects (n = 6). Mean resting basal catecholamine values were similar in the three groups. One min standing elicited an increase in norepinephrine plasma level (but not in epinephrine plasma levels) in control group but not in diabetic patients (with or without orthostatic hypotension). The maximal number of platelet alpha 2-adrenoceptors (and Kd) calculated by [3H]-yohimbine saturation experiments was similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in high affinity state determined by inhibition experiments of [3H]-yohimbine binding by UK14,304 (a specific alpha 2-adrenergic full agonist) was significantly lower in diabetic patients with orthostatic hypotension (29.2 +/- 5.3%) than in the other two groups. No significant difference was found between the control group (60.0 +/- 2.0%) and diabetic patients without orthostatic hypotension (64.3 +/- 3.1%). These results indicate that orthostatic hypotension in insulin-dependent diabetic patients is marked by a lack of noradrenaline increase in standing position and by a decrease in platelet alpha 2-adrenoceptors in high affinity state. Thus we suggest that orthostatic hypotension of diabetes mellitus is the result of sympathetic nerves injuries and of abnormalities in alpha 2-adrenoceptors coupling.

Autonomic Nervous System Diseases↗

PubMed1989

Recent advances in the pharmacology of rilmenidine.

The antihypertensive properties of rilmenidine, an oxazoline derivative, have been demonstrated in several experimental models of hypertension after short- or long-term administration. In pentobarbitone-anesthetized spontaneously hypertensive rats, intravenous rilmenidine (0.1 to 1 mg/kg) dose-dependently reduced blood pressure and heart rate. Upon long-term subcutaneous infusion (5 to 15 mg/kg per day) in conscious spontaneously hypertensive rats, rilmenidine induced a dose-dependent decrease in both cardiovascular parameters. In conscious sino-aortic denervated dogs, rilmenidine (1 mg/kg orally for two weeks) significantly reduced blood pressure and heart rate. The hypotensive action of rilmenidine is mediated through a reduction in peripheral sympathetic tone, resulting from a central action and possibly a peripheral action. Rilmenidine also decreases catecholamine release from the adrenal medulla which might contribute to the antihypertensive effect. Therefore, rilmenidine acts similarly to clonidine and related compounds in order to lower blood pressure, i.e., reduction of sympathetic tone. Nevertheless, although it binds to alpha 2-adrenoceptors, rilmenidine did not cause sedation in animal models: at doses up to 10 mg/kg in mice and rats, it did not prolong the barbiturate-induced sleeping time and did not modify the spontaneous locomotor activity in rats at doses up to 2.5 mg/kg. These results demonstrate a dissociation between sedative and antihypertensive effects of rilmenidine. Three hypotheses have been proposed to explain why this drug is almost devoid of sedative activity in animal experimental models: (1) unknown properties counteracting the alpha 2-adrenoceptor-mediated sedation; (2) a preferential action at the peripheral level; (3) central receptors involved in sedation and hypotension may be different. The intimate mechanism underlying the hypotensive effects of rilmenidine is currently under investigation. The evidence for rilmenidine binding on central sites named "imidazoline sites" involved in blood pressure regulation could possibly provide further insight into its mechanism of action and explain the duality of its effects.

Adrenergic alpha-Agonists↗

PubMed1989

Effect of apomorphine on adrenal medullary catecholamine levels.

The effects of the dopamine receptor agonist, apomorphine, on the total catecholamine content of the adrenal medulla were studied in normotensive rats. Apomorphine (3, 15, 30 mg/kg SC) induced a dose-dependent decrease in catecholamine content of the adrenal gland. The action of apomorphine was suppressed by previous treatment with the non specific dopamine receptor antagonist, haloperidol (9 mg/kg IP), or the D2 antagonist domperidone (2 mg/kg IP), but not by the D1 antagonist SCH 23390 (1 mg/kg IP). The apomorphine-induced decrease in adrenal catecholamine concentration was suppressed by denervation of the adrenal medulla, i.e. unilateral section of splanchnic fibers performed 5 days before. These results show that, under our experimental conditions, the effect of apomorphine is due to the activation of D2 dopamine receptors probably located on splanchnic nerve endings and suggest the existence of a peripheral D2 dopaminergic system which modulates adrenal medullary catecholamine content.

Adrenal Medulla↗

PubMed1989

Lipomobilizing effects of procaterol and yohimbine in the conscious dog: comparison of endocrinological, metabolic and cardiovascular effects.

1. Lipid mobilization during a hypocaloric diet may be enhanced by a pharmacological approach using beta 2-adrenoceptor agonists or alpha 2-adrenoceptor antagonists. Studies were undertaken in the dog, an animal model presenting fat cell antilipolytic alpha 2- and lipolytic beta-adrenoceptors, in order, firstly, to demonstrate the presence of beta 2 subtype adrenoceptors on adipocytes and, secondly, to compare the effects of procaterol (beta 2-adrenoceptor agonist) and of yohimbine (alpha 2-adrenoceptor antagonist) on metabolic, endocrinological and cardiovascular parameters. 2. Procaterol strongly stimulates lipolysis in dog adipocytes in vitro. The utilisation of selective beta 1- and beta 2-adrenoceptor antagonists (bisoprolol and ICI 118,551) in both lipolysis and binding studies (displacement of [3H]-dihydroalprenolol binding) demonstrated the presence of the two beta-adrenoceptor subtypes in dog fat cells. 3. Infusion of either yohimbine or procaterol (10 and 0.4 nmol min-1 kg-1, respectively for 30 min), provoked an equivalent increase in plasma non-esterified fatty acids (+100%). Procaterol, but not yohimbine, induced hyperglycaemia (+120%). Plasma insulin was weakly enhanced by yohimbine (+120%) as compared to the increase given by procaterol (+500%). 4. Both drugs stimulated sympathetic nervous system activity, as indicated by the increased plasma noradrenaline concentration, but only yohimbine increased the plasma adrenaline level. 5. Cardiovascular measurements indicated that procaterol strongly enhances heart rate and transiently decreases mean blood pressure. Yohimbine exhibits a weaker effect on heart rate and slightly increases mean blood pressure. 6. The present work clearly indicates that lipid mobilization is enhanced during fasting in the dog by selective beta 2-adrenoceptor stimulation or by alpha 2-adrenoceptor blockade. This enhanced lipolytic effect may result either from a direct action of the drugs on the adrenoceptors of fat cells or from an activation of the sympathetic nervous system. Procaterol suffers major limitations since it strongly increases heart rate, immunoreactive insulin and glycaemia. On the other hand, yohimbine induces only minor modifications both in cardiovascular and endocrinological parameters.

Adipose Tissue↗

PubMed1989

Effects of pinacidil on the sympatho-adrenal system in dogs.

1. The aim of the present work was to study the antihypertensive effect of pinacidil, a potassium channel opener, in sinoaortic denervated (SAD) conscious dogs and to investigate whether the involvement of the sympathetic nervous system induced by this vasodilator compound is only of baroceptor reflex origin. 2. Pinacidil (0.1, 0.2, 0.4 mg kg-1 i.v.) induced a dose-dependent decrease in blood pressure in normal as well as in SAD dogs. In contrast, the induced-tachycardia observed in normal dogs was not found in SAD animals. 3. Since pinacidil induced an increase in plasma catecholamines, free fatty acids, glucose, plasma renin activity and aldosterone in SAD dogs it is suggested that this sympathetic activation is independent of the baroreceptor reflex pathways. 4. The sympathetic activation is mainly of peripheral origin, since pinacidil (0.7 mg kg-1 i.v.) induced an increase in adrenaline release from the adrenal gland after section of the great splanchnic nerve in anaesthetized dogs. This increase is probably due to an effect that does not involve K+ channel opening. However, this effect of pinacidil was not observed during splanchnic nerve stimulation (in this case, the involvement of K+ channel opening is suggested).

Adrenal Glands↗

PubMed1989

Effects of verapamil on sympathetic tone in normal and chronic sinoaortic-denervated conscious dogs.

Previous studies have shown that calcium channel blockers from the dihydropyridine group (such as nicardipine) induce an increase in sympathetic tone from a central origin in chronic sinoaortic-denervated (SAD) dogs. In the present study, we investigated to see if verapamil possesses such properties. The effects of acute injection of verapamil (0.2 mg/kg i.v.) were compared in normal and SAD conscious dogs. Verapamil induced a decrease in blood pressure in the two groups of animals, and an increase in heart rate and plasma catecholamines (noradrenaline and adrenaline) in normal but not in SAD dogs. Contrary to the dihydropyridine studies (nicardipine), we did not find any evidence for a centrally mediated sympathoexcitatory effect of verapamil in conscious SAD dogs.

Animals↗

PubMed1989

[Cicletanine and the sympathetic nervous system. A study of awake sino-aortic denervated hypertensive dogs].

The antihypertensive action of non diuretic doses of cicletanine, a new antihypertensive compound, has been studied in neurogenic hypertensive dogs. Four months after sinoaortic denervation, Fourteen dogs were randomly allocated into two parallel groups of oral treatment: cicletanine (10 mg/kg/12 h (n = 7)) or placebo (n = 7). Urinary parameters (diuresis, urinary sodium, potassium, urea and creatinine clearance), cardiovascular parameters (blood pressure (BP) and heart rate) and sympathetic tone (noradrenaline and adrenaline plasma levels) were measured before and after one month of treatment in conscious animals. Chronic treatment with cicletanine lowered BP in neurogenic hypertensive dogs (204 +/- 10/116 +/- 5 mmHg before and 159 +/- 12/86 +/- 8 mmHg after treatment) without any diuretic effect. Cicletanine failed to modify plasma noradrenaline (457 +/- 100 pg/ml versus 419 +/- 135 pg/ml) or adrenaline (213 +/- 36 pg/ml versus 166 +/- 35 pg/ml). These data confirm that cicletanine exerts antihypertensive actions which are independent of its natriuretic properties. Moreover, they suggest that the decrease in arterial blood pressure does not involve sympathetic pathways.

Animals↗

PubMed1989

[Current data on the pharmacology of rilmenidine].

Oral rilmenidine (1 mg/kg/day for 2 weeks) significantly reduces the blood pressure and heart rate of conscious barodenervated dogs. A dose-dependent decrease in blood pressure and heart rate has been demonstrated with intraveinous rilmenidine (0.1 to 1 mg/kg) in pentobarbitone anaesthetised spontaneously hypertensive rats (SHR). Chronic subcutaneous administration of rilmenidine (5 to 15 mg/kg/day) also produces a dose-dependent decrease of these two parameters in conscious SHR. In addition, rilmenidine reduces plasma noradrenaline and the liberation of catecholamines from the adrenal medulla; these actions could contribute to its antihypertensive effect. The hypotensive effect of rilmenidine, clonidine and related molecules, is due to a reduction in sympathetic tone of central or peripheral origin. Although rilmenidine binds to alpha-2 adrenergic receptors, it does not cause sedation in animal models: it does not prolong barbiturate-induced sleep in the mouse and rat at doses of up to 10 mg/kg and does not affect spontaneous locomotor activity in the rat at doses of up to 2.5 mg/kg. The results show a dissociation of the sedative and antihypertensive effects of rilmenadine. The almost complete absence of sedation in animal models may be explained by: as yet unknown properties inhibiting sedation, a preferential peripheral site of action and/or the presence of separate central receptors accounting for the sedative or hypotensive effects. The precise mechanism of the hypotensive effects of rilmenidine is currently under study. The binding of rilmenidine at central "imidazoline receptor" sites responsible for the regulation of the blood pressure could explain its mode of action and why its pharmacological profile is different to that of other centrally acting hypotensive agents.

Animals↗

PubMed1989

Differential regulation of fat cell beta-2 and beta-1 adrenoceptors by endogenous catecholamines in dog.

The effects of long-term endogenous catecholamine exposure on the regulation of leukocyte and adipocyte beta adrenoceptor subtypes were studied through an experimental model of chronic neurogenic hypertension in the dog. Chronic sinoaortic denervation (SAD) is associated with a significant increase in plasma catecholamine levels, a reduction in the total beta adrenoceptor number of the leukocytes (52%) as well as of the omental adipocytes (59%). Using highly selective beta antagonists (bisoprolol for beta-1; ICI 118,551 for beta-2 adrenoceptors) we demonstrate that the normal dog fat cell possess both beta-2 and beta-1 adrenoceptors in proportions of 67 and 33%, respectively. SAD-induced catecholamine enhancement promotes a strong reduction of beta-2 (but not beta-1) adrenoceptor number (from 237 +/- 28 to 52 +/- 13 fmol/mg of protein) leading to a new relative distribution in fat cell membranes: 36% for beta-2 and 64% for beta-1 adrenoceptors. Such a different regulation provokes major consequences in the associated-biological effect on adipocytes when evaluating the lipolytic process. Lipolysis induced by epinephrine or isoproterenol (two mixed agonists) is weakly but significantly reduced whereas lipolysis induced by procaterol (a highly selective beta-2 agonist) is strongly reduced. These data fit with the results of the binding studies and demonstrate the loss in beta-2 adrenoceptor number and efficiency in SAD dogs. The present study demonstrates a differential regulation of beta adrenoceptors: beta-2 but not beta-1 adrenoceptors are decreased by long-term exposure to high plasma levels of endogenous catecholamines in the dog.

Adipose Tissue↗

PubMed1989

[Alpha 2-adrenergic receptors and arterial pressure].

The aim of this work was to investigate the influence of blood pressure levels on human platelet alpha 2-adrenergic receptivity. The study was carried out on 12 mild essential hypertensive patients and 7 normotensive parkinsonians with orthostatic hypotension. Alpha 2-adrenoceptors number and affinity were determined by 3H-yohimbine binding, plasma catecholamines were measured by HPLC and adrenaline-induced platelet aggregation by turbidimetry. Results obtained were compared with those of two groups of 12 normotensive control subjects. In hypertensive patients, both platelet alpha 2-adrenoceptors (139 +/- 6 vs 176 +/- 18 fmol/mg protein) and velocity of adrenaline-induced platelet aggregation were decreased whereas plasma adrenaline and noradrenaline remained unchanged. In patients with orthostatic hypotension, there was an increased number of platelet alpha 2-adrenoceptors (313 +/- 52 vs 168 +/- 8 fmol/mg protein) associated with a significant decrease in plasma noradrenaline (62 +/- 11 vs 190 +/- 25 pg/ml). In none of the two groups of patients there was any change in receptor affinity for 3H-yohimbine. These results indicate that human platelet alpha 2-adrenoceptors levels are related to blood pressure values. Moreover, up-regulation in orthostatic hypotension and lack of down-regulation in essential hypertension suggest that only sustained abnormal plasma noradrenaline levels could allow the development of alpha 2-adrenoceptors regulatory mechanisms. These variations can represent tentative compensatory mechanisms for normalization of blood pressure levels.

Aged↗

PubMed1988

Rilmenidine (S 3341) and the sympathoadrenal system: adrenoreceptors, plasma and adrenal catecholamines in dogs.

1. The effects of rilmenidine, a new alpha 2-adrenoreceptor agonist with antihypertensive properties, were investigated on plasma catecholamines, blood cell adrenoreceptors and adrenal medullary function. 2. In conscious sino-aortic denervated (SAD) dogs, rilmenidine (1 mg kg-1 orally for 2 weeks) significantly reduced both blood pressure and heart rate when compared with placebo treatment. The drug decreased plasma noradrenaline and adrenaline levels and corrected the decrease in leucocyte beta-adrenoreceptors observed in placebo-treated SAD dogs. There was no change in platelet alpha 2-adrenoreceptors. 3. In anaesthetized normotensive dogs, rilmenidine (0.1 and 0.3 mg kg-1 i.v.) induced a dose-dependent decrease in both cardiovascular parameters (blood pressure and heart rate) and catecholamine release from the adrenal medulla. 4. The present study shows that rilmenidine decreases sympathetic tone mainly by an action on the adrenal medulla. In addition, its ability to lower blood pressure in SAD dogs, i.e. a model of hypertension in which high sympathetic tone is present, indicates that rilmenidine may also depress other parts of the sympathetic nervous system.

Adrenal Medulla↗

PubMed1988

Is adrenal medulla involved in the antihypertensive effect of nicardipine?

The effects of nicardipine, a dihydropyridine calcium channel blocker, on adrenal medulla were investigated in chloralose-anesthetized dogs. For analysis of the adrenal medullary function, adrenal venous catecholamine rates were determined. Intravenous administration of nicardipine (50 micrograms/kg) induced a marked increase in both adrenal catecholamine rates and heart rate and a simultaneous decrease in blood pressure. This effect on epinephrine and norepinephrine release is probably explained by the involvement of baroreflex mechanisms. After acute splanchnicectomy, nicardipine (50 and 100 micrograms/kg i.v.) failed to modify catecholamine secretion rates from the denervated adrenal medulla during electrical stimulation of the splanchnic nerve at low (2 Hz) and high (5 Hz) frequencies. In conclusion, these results suggest that in vivo a functional dihydropyridine-sensitive calcium channel is not required for calcium entry mechanisms into dog chromaffin cells. Moreover, adrenal medulla is not involved in the antihypertensive action of nicardipine.

Adrenal Medulla↗

PubMed1987

Chronic chlorimipramine does not reverse the reduction of cerebrospinal fluid Met-enkephalin-like immunoreactivity in chronic-pain patients.

Chronic-pain patients were treated for 10 days with chlorimipramine (100 mg i.v. daily), and their plasma levels of the drug and cerebrospinal fluid (CSF) levels of Met-enkephalin-like material (MELM) were measured for a comparison with those found in untreated chronic-pain patients and in control subjects. Pain relief in chlorimipramine-treated patients was apparently not associated with pronounced changes in the activity of enkephalinergic systems since the mean CSF levels of MELM were reduced to the same extent in treated (-49%) and untreated (-45%) pain patients as compared with controls. However, subtle chlorimipramine-induced alterations likely occurred as revealed by the simultaneous measurement of the CSF levels of 5-hydroxyindoleacetic acid (5-HIAA) in the same patients. Indeed, a positive correlation (r = 0.667) was found between CSF 5-HIAA and MELM levels in control subjects, whereas a negative correlation (r = 0.691) between these two parameters was detected in chlorimipramine-treated patients. These data suggest that chlorimipramine alters probable functional serotonin-enkephalin interactions in pain patients.

Adult↗