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Biomedical subjects

I Macquin-Mavier

Publications and source records attributed to I Macquin-Mavier.

At least 37 records · Page 2Linked to original sources
PubMed1993

Involvement of tachykinins in pentamidine-induced airway constriction and microvascular leakage in the guinea pig.

We investigated the effects of aerosolized pentamidine isethionate on airway constriction and microvascular leakage in the guinea pig, and the role of tachykinins in these abnormalities. The bronchoconstrictor response to pentamidine was determined in anesthetized, tracheotomized and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized pentamidine (5 to 30 mg/ml; 60 breaths). Respiratory system resistance was measured by the occlusion method. Airway microvascular permeability was evaluated by measuring the Evans blue dye concentration in the trachea and main bronchi. Aerosolized pentamidine caused a concentration-related increase in respiratory system resistance that was prevented by pretreatment with 50 mg/kg capsaicin given subcutaneously 2 wk before pentamidine and was significantly reduced by pretreatment with 1 mg/kg morphine given intravenously. Pretreatment with 10(-4) M aerosolized phosphoramidon (90 breaths) significantly enhanced the bronchoconstrictor response to pentamidine. Aerosolized pentamidine (50 mg/ml; 90 breaths) increased airway microvascular permeability, as the Evans blue dye concentration was 72.6 +/- 3.7 ng/mg tissue in guinea pigs aerosolized with pentamidine versus 34.2 +/- 3.5 ng/mg tissue in the controls. Capsaicin pretreatment inhibited the increase in microvascular leakage induced by pentamidine. Pretreatment with 5 mg/ml aerosolized albuterol (90 breaths) prevented the bronchoconstrictor response to pentamidine but failed to prevent the pentamidine-induced increase in microvascular permeability. Atropine did not modify the bronchoconstrictor response to pentamidine. These results indicate that in the guinea pig, pentamidine isethionate induces bronchoconstriction and airway microvascular leakage, which are mediated by tachykinins released from sensory nerves. Albuterol, which is used in humans to prevent bronchoconstriction, does not seem able to prevent airway edema.

Aerosols↗
PubMed1992

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

High impedance mechanical ventilator for small animals: use of programmable controller.

We built a simple high impedance ventilator, which generates a pattern of flow largely independent of respiratory mechanics, to mechanically ventilate anaesthetized small animals. The system includes a source of compressed gas with an electronic valve and a flow controller on the inspiratory side and a second valve on the expiratory side. The two valves are driven by a programmable controller. To assess the performance of this ventilator we measured the delivered tidal volume while the ventilator was connected to an external, gradually varying resistance. This resistance was progressively increased to simulate bronchoconstriction of the respiratory system. Comparison with a volume-controlled ventilator was made. The use of a programmable controller also allows control of different patterns of mechanical ventilation, such as end-inspiratory pause or the static pressure-volume relationship, which can be used to perform lung function tests. The system is a simple, versatile device allowing both reliable mechanical ventilation and lung function assessment in small rodents and is suitable for routine use in laboratories.

Animals↗
PubMed1992

Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive heart failure.

The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent both right and left catheterization. Haemodynamic parameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1 in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than 0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of neuraminidase on airway reactivity in the guinea pig.

We investigated the effects of neuraminidase, a viral enzyme that cleaves alpha ketosidic cell-bound sialic acids, to see if it accounts for parainfluenza and influenza virus-induced airway hyperreactivity. Accordingly, Vibrio cholerae neuraminidase was administered intratracheally in guinea pigs, and airway reactivity was assessed 3 h later. Removal of sialic acid residues was evaluated by histologic studies. Airway responsiveness was determined in anesthetized, tracheotomized, and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized bronchoconstrictor agents. Respiratory system conductance was measured by the occlusion method. Neuraminidase injected intratracheally did not change airway reactivity to 10(-4) to 10(-2) M acetylcholine or 10(-4) to 2.5 x 10(-3) M histamine; nor did it prevent aerosolized albuterol from inhibiting histamine-induced bronchoconstriction. Substance P (10(-6) to 5 x 10(-5) M) had no significant bronchoconstrictor effect on guinea pigs pretreated with saline or neuraminidase. In guinea pigs pretreated with aerosols of the neutral endopeptidase inhibitor phosphoramidon (10(-4) M) before the concentration curve to aerosolized substance P was recorded, neuraminidase significantly reduced substance P-induced bronchoconstriction. When bronchoconstriction was induced by the 4-11 fragment of substance P (10(-5) to 10(-2) M), which is devoid of positive charges, it did not differ significantly in guinea pigs pretreated with saline and those pretreated with neuraminidase. These results indicate that in the guinea pig, neuraminidase injected intratracheally does not induce non-specific airway hyperreactivity and may alter the binding of substance P to its receptors.

Albuterol↗
PubMed1992

Effect of thoracic epidural anesthesia combined with general anesthesia on segmental wall motion assessed by transesophageal echocardiography.

Patients scheduled for vascular surgery are considered at risk for perioperative cardiac complications. Choice of anesthetic in such patients is guided by a desire not to adversely affect myocardial function. On the basis of data from laboratory studies, thoracic epidural anesthesia (TEA) has been advocated to prevent myocardial ischemia. The aim of this study was to assess whether TEA combined with general anesthesia has any effect on segmental wall motion (SWM) monitored by transesophageal echocardiography in these patients. Patients received alfentanil, midazolam, vecuronium, and 50% N2O in oxygen, and ventilation was controlled after orotracheal intubation; 12.5 mL of 2% lidocaine HCl was injected through an epidural catheter placed at T6-7 or T7-8. Hemodynamic measurements and transesophageal echocardiographic recordings were obtained before and 10, 20, 30, 40, and 60 min after lidocaine injection. Segmental wall motion was graded a posteriori by two independent experts on a predetermined scale (from 1 = normal to 5 = dyskinesia). A decrease greater than or equal to 2 grades was considered an SWM abnormality indicative of ischemia. Thoracic epidural anesthesia induced a decrease in systemic arterial blood pressure, heart rate, and cardiac index. The SWM score decreased slightly from 1.34 +/- 0.68 to 1.27 +/- 0.64 (mean +/- SD) (at 10 and 20 min, respectively) (P less than 0.05). Patients were a posteriori analyzed according to whether they had documented coronary artery disease or not. The SWM score before TEA was significantly higher in patients with documented coronary artery disease (1.51 +/- 0.88 vs 1.17 +/- 0.51, respectively; P less than 0.05) and did not change significantly after TEA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Effects of platelet-activating factor on lung epithelial permeability in the guinea-pig.

We examined the effects of platelet-activating factor (PAF) on lung epithelial permeability by measuring the clearance of intratracheally administered 99m-technetium-labeled diethylene triamine penta-acetic acid (99mTc-DTPA) in guinea-pigs which were anaesthetised, paralysed and mechanically ventilated. The clearance of the radiolabeled tracer molecule 99mTc-DTPA from airways to the blood was expressed as changes in counts/min corrected for background. For each guinea-pig, 99mTc-DTPA clearance was assessed before and after i.v. PAF administration, when tracheal pressure had returned to near control values. Doses of 10, 50 and 100 ng/kg of PAF caused dose-dependent increases in 99mTc-DTPA clearance of 7 +/- 3%, 38 +/- 7% and 65 +/- 11% respectively. The respective effects of 0.5 mg/kg of the beta 2-adrenergic agonist salbutamol and 0.3 mg/kg of the alpha 1-adrenergic agonist methoxamine on the increase in lung epithelial permeability induced by 50 ng/kg PAF were also studied. Salbutamol significantly reduced the acute bronchoconstrictor effects of PAF, but did not affect the increase in lung epithelial permeability, which was 58 +/- 10%. Conversely, methoxamine significantly enhanced the bronchoconstrictor effects of PAF but inhibited the lung epithelial permeability increase, which was only 10 +/- 13%. In the absence of PAF, salbutamol significantly increased this permeability by 49 +/- 11%, whereas methoxamine alone slightly reduced, it by -11 +/- 4%. These results demonstrate that PAF increases lung epithelial permeability and suggest that vascular surface area recruitment may explain this increase.

Albuterol↗
PubMed1991

Effects of clonidine on variation of arterial blood pressure and heart rate during carotid artery surgery.

The effect of oral premedication with 300 micrograms of clonidine on systemic arterial pressure, heart rate, and plasma norepinephrine levels was assessed in a double-blinded, placebo-controlled study conducted in 29 patients subjected to carotid artery surgery (CAS). Anesthesia was induced with thiopental, 6 mg/kg, and alfentanil, 0.05 mg/kg, and maintained with alfentanil and 0.6% isoflurane in 50% N20/O2. The study was divided into five periods as follows: (1) anesthesia to start of surgery; (2) surgery to carotid artery clamping; (3) carotid artery clamping to unclamping; (4) carotid artery unclamping to the end of surgery; and (5) the first 4 postoperative hours in the recovery room. In the clonidine group (n = 14), plasma norepinephrine concentrations were significantly lower before induction of anesthesia and during the operative period. Heart rate and systemic arterial pressure were lower (P less than 0.01) in the clonidine group at 3 different time intervals (control, carotid clamping, carotid unclamping). However, during each of the previously defined periods, the variability of heart rate and systemic arterial pressure, assessed by the coefficient of variation, was not different between the two groups. The lability of these hemodynamic parameters, expressed as the percentage of values, which increased or decreased more than 20% of control values during the corresponding period, was also comparable between the two groups. The number of patients who experienced at least one episode of hypertension (systolic arterial pressure greater than 180 mm Hg), hypotension (systolic arterial pressure less than 100 mm Hg), or bradycardia less than 45 beats/min was not different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

5-Hydroxytryptamine-induced bronchoconstriction in the guinea-pig: effect of 5-HT2 receptor activation on acetylcholine release.

1. The bronchoconstrictor responses to 5-hydroxytryptamine (5-HT) were studied in the guinea-pig to establish whether they are partly attributable to parasympathetic activation within the airways. 5-HT dose-response curves were constructed in anaesthetized and ventilated guinea-pigs pretreated with saline, or by bilateral cervical vagotomy or vagotomy plus atropine 3 mg kg-1, i.v. Vagotomy had no effect on 5-HT-induced bronchoconstriction but vagotomy plus atropine significantly reduced it. 2. To determine whether parasympathetic activation within the airways resulted from pre- or postganglionic stimulation, 5-HT dose-response curves were constructed for two groups of vagotomized guinea-pigs treated with hexamethonium 2 mg kg-1, or hexamethonium 2 mg kg-1, plus atropine 3 mg kg-1. Guinea-pigs treated with hexamethonium plus atropine experienced significantly less 5-HT-induced bronchoconstriction than those treated with hexamethonium alone. 3. To characterize the subtype of 5-HT receptors involved in the activation of the parasympathetic system by 5-HT, dose-response curves to 5-HT were constructed for four groups of vagotomized guinea-pigs treated with saline, 1 mg kg-1 of the 5-HT3 antagonist ICS 205-930, or either 0.01 or 0.1 mg kg-1 of the 5-HT2 antagonist ketanserin. ICS 205-930 enhanced 5-HT-induced bronchoconstriction but 0.01 mg kg-1 ketanserin inhibited it significantly and 0.1 mg kg-1 ketanserin abolished it. To confirm the involvement of 5-HT2 receptors in these responses, we studied the effects in vagotomized guinea-pigs of atropine on the bronchoconstriction induced by the 5-HT2 agonist,x alpha-methyl-5-HT, infused at rates of 40 and 80ngkg-1s-'. At both rates, atropine significantly reduced the bronchoconstrictor responses to alpha-methyl-5-HT. 4. The above results indicate that 5-HT-induced bronchoconstriction is indeed partly mediated by parasympathetic activation within the airways. This activation is mediated by stimulation of 5-HT2 receptors which are probably located on the postganglionic parasympathetic nerve endings.

Acetylcholine↗
PubMed1991

Hormonal interactions and renal function during mechanical ventilation and ANF infusion in humans.

To investigate the influence of atrial natriuretic factor (ANF) on renal function during mechanical ventilation (MV), we examined the renal and hormonal responses to synthetic human ANF infusion in eight patients during MV with zero (ZEEP) or 10 cmH2O positive end-expiratory pressure (PEEP). Compared with ZEEP, MV with PEEP was associated with a reduction in diuresis (V) from 208 +/- 51 to 68 +/- 11 ml/h (P less than 0.02), in natriuresis (UNa) from 12.4 +/- 3.3 to 6.2 +/- 2.1 mmol/h (P less than 0.02), and in fractional excretion of sodium (FENa) from 1.07 +/- 0.02), 0.21 to 0.67 +/- 0.17% (P less than 0.02) and with an increase in plasma renin activity (PRA) from 4.83 +/- 1.53 to 7.85 +/- 3.02 ng.ml-1.h-1 (P less than 0.05). Plasma ANF levels markedly decreased during PEEP in four patients but showed only minor changes in the other four patients, and mean plasma ANF levels did not change (163 +/- 33 pg/ml during ZEEP and 126 +/- 30 pg/ml during PEEP). Glomerular filtration rate and renal plasma flow were unchanged. Infusion of ANF (5 ng.kg-1.min-1) during PEEP markedly increased V and UNa by 110 +/- 61 and 107 +/- 26%, respectively, whereas PRA decreased from 7.85 +/- 3.02 to 4.40 +/- 1.5 ng.ml-1.min-1 (P less than 0.05). In response to a 10 ng.kg-1.min-1 ANF infusion, V increased to 338 +/- 79 ml/h during ZEEP but only to 134 +/- 45 ml/h during PEEP (P less than 0.02), whereas UNa increased, respectively, to 23.8 +/- 5.3 and 11.3 +/- 3.3 mmol/h (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Pulmonary vascular response to endothelin in rats.

This study investigated the pulmonary vascular response to endothelin (ET) in rats. In conscious rats, an incremental intravenous bolus of ET-1 (100-1,000 pM) caused, after an initial drop in systemic arterial pressure (Psa), a secondary dose-dependent increase of Psa concomitant with a decrease of cardiac output (CO) and heart rate (HR). Pulmonary arterial pressure (Ppa) remained unchanged, and pulmonary vascular resistance (PVR) increased significantly only after 1,000 pM (+ 40.0 +/- 10.4 at 15 min). Meclofenamate (6 mg/kg iv) did not alter hemodynamic response to ET (300 pM). After autonomic blockade with hexamethonium (6 mg/kg iv) plus atropine (0.75 mg/kg iv), bradycardia response to ET (300 pM) was blocked, but CO decreased, systemic vascular resistance increased, and PVR remained unchanged as in controls. In anesthetized ventilated rats, bolus injections of ET (10-1,000 pM) induced a transient dose-related decrease in compliance (-10.9 +/- 1.8% after 1,000 pM) but no change of conductance. In isolated lungs, Ppa increased at doses greater than 100 pM, and edema developed in response to 1,000 pM ET. The rise of Ppa in response to 300 pM was not altered by meclofenamate (3.2 x 10(-6) M) but was potentiated by inhibitors of endothelium-derived relaxing factor(s) (EDRF), methylene blue (10(-4) M), pyrogallol (3 x 10(-5) M), and NG-monomethyl-L-arginine (6 x 10(-4) M) (3.9 +/- 0.3, 4.6 +/- 0.5, and 5.9 +/- 0.3 mmHg, respectively, compared with 1.5 +/- 0.5 mmHg in control lungs). These results suggest that circulating ET is a more potent constrictor of the systemic circulation than of the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Droperidol prevents serotonin-induced bronchospasm in the guinea pig.

The effects of droperidol on bronchoconstriction induced by serotonin (5-HT) were studied in mechanically ventilated, paralyzed guinea pigs that had been anesthetized with pentobarbital. Droperidol did not modify the resting bronchial tone but prevented the bronchoconstrictor effects of 5-HT in a dose-related manner. Pretreatment with propranolol, hexamethonium, or prazosin did not alter the protective effects of droperidol on 5-HT-induced bronchoconstriction. The bronchoconstrictor responses to histamine or acetylcholine were not affected by droperidol. These results suggest that the protective effects of droperidol on 5-HT-induced bronchoconstriction are mediated through 5-HT receptor blockade on bronchial smooth muscle.

Acetylcholine↗
PubMed1991

Deliberate hypotension with nicardipine or nitroprusside during total hip arthroplasty.

To induce deliberate hypotension during anesthesia, nicardipine was administered to patients undergoing total hip arthroplasty and was randomly compared with nitroprusside. Hemodynamic measurements were performed before and 10, 20, 30, and 60 min after starting to administer either nicardipine (n = 12) or nitroprusside (n = 12) (B, T1, T2, T3, and T4, respectively); at the end of drug infusion (T5); and 10, 20, and 60 min later (T6, T7, and T8, respectively). Plasma renin activity and catecholamine levels were measured at B, T1, T5, T6, and T7. In addition, plasma nicardipine concentration was measured in five patients at T1, T2, T5, T7, and T8. As with nitroprusside, nicardipine administration (1-3 micrograms.kg-1.min-1, after a titration dose of 4.7 +/- 1.5 mg) resulted in hypotension (up to -34% +/- 3%), a decrease in systemic vascular resistances (up to -49% +/- 4%), and increases in heart rate (up to +17% +/- 6%), cardiac index (up to +37% +/- 8%), plasma norepinephrine (up to +63% +/- 17%) and epinephrine (up to +232% +/- 68%) levels, and plasma renin activity (up to +336% +/- 207%). Ten and 20 minutes after discontinuation of the hypotensive drug, nicardipine led to persistent vasodilation and hypotension, which differed significantly from the hypertensive rebound observed after nitroprusside discontinuation, despite a similar increase in plasma renin activity and catecholamine levels. Our results indicate that after the infusion was terminated, the nicardipine-induced vasodilation was opposed to the vasoconstrictive effects of angiotensin II and catecholamines, thus avoiding hypertensive rebound.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Influence of lung volume on histamine-induced bronchoconstriction in guinea-pigs.

The influence of lung volume on bronchopulmonary reactivity was investigated in 4 groups of 14 anaesthetized paralysed mechanically ventilated guinea-pigs: animals of group 1 served as control; in animals of group 2, the parasympathetic nervous system was blockaded with atropine; animals of group 3 were submitted to a bilateral cervical vagotomy; animals of group 4 were both vagotomized and pretreated with atropine. In each group, the animals were randomly divided into 2 subgroups: one was ventilated at zero end-expiratory pressure (ZEEP), the other with 0.2 kPa positive end-expiratory pressure (PEEP) resulting in a mean increase in lung volume of about 1 ml. Bronchopulmonary response to infused histamine was assessed by the respiratory conductance and compliance values measured during bronchoconstriction (respectively HGrs and HCrs). In the control group, animals exposed to PEEP were found significantly less reactive than those ventilated at ZEEP. In groups 2, 3 and 4, this difference was significantly reduced for HGrs and even abolished for HCrs. These results demonstrate that the effect of lung volume on moderate histamine-induced bronchoconstriction in guinea-pigs is not purely mechanical, but is partly vagally mediated. They also suggest that this vagally mediated inhibitory influence results from involvement of central reflexes evoked by stretch receptor stimulation.

Animals↗
PubMed1990

Influence of tidal volume on histamine-induced bronchoconstriction in guinea pigs.

The effects of tidal volume amplitude on bronchopulmonary reactivity were investigated in three groups of 14 anesthetized paralyzed mechanically ventilated guinea pigs. Animals of group 1 served as control; in animals of group 2, both the sympathetic and parasympathetic nervous systems were blocked; in animals of group 3, only the parasympathetic system was blocked. In each group, the animals were randomly divided into two subgroups characterized by their ventilatory pattern: rate of 60/min with a 6-ml/kg tidal volume or rate of 40/min with a 9-ml/kg tidal volume. Bronchopulmonary reactivity to infused histamine was assessed by the respiratory compliance and conductance values measured during bronchoconstriction and expressed as a percentage of the corresponding basal values. In group 1 the animals ventilated with a 9-ml/kg tidal volume were found significantly less reactive than those ventilated with a 6-ml/kg tidal volume. This difference was abolished in groups 2 and 3. These results demonstrate that the effects of increased tidal volume on bronchopulmonary reactivity are vagally mediated and suggest that the decrease observed in histamine-induced bronchoconstriction is mainly due to reflex effects evoked by stretch receptor stimulation.

Animals↗
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↗