Propranolol causes a paradoxical enhancement of cardiomyocyte foetal gene response to hypertrophic stimuli.

Background And Purpose: Pathological cardiac hypertrophy is associated with the expression of a gene profile reminiscent of foetal development. The non selective beta-adrenoceptor antagonist propranolol is able to blunt cardiomyocyte hypertrophic response in pressure-overloaded hearts. It remains to be determined whether propranolol also attenuates the expression of hypertrophy-associated foetal genes.

Pressure overload causes cardiac hypertrophy in beta1-adrenergic and beta2-adrenergic receptor double knockout mice.

Objective: Cardiac hypertrophy arises as an adaptive response to increased afterload. Studies in knockout mice have shown that catecholamines, but not alpha1-adrenergic receptors, are necessary for such an adaptation to occur. However, whether beta-adrenergic receptors are critical for the development of cardiac hypertrophy in response to pressure overload is not known at this time.

A new method of orotracheal intubation in mice.

A new method of orotracheal intubation in mice is described. After intraperitoneal induction of anaesthesia, 36 male animals, belonging to common laboratory strains, have been intubated with the aid of a straight, small bore arthroscope, connected to a video-camera. After the insertion of a guide wire of appropriate size across the vocal cords, a polyethylene (PE) cannula has been introduced over it as an endotracheal tube.

Na+/H+ exchange inhibition attenuates left ventricular remodeling and preserves systolic function in pressure-overloaded hearts.

Cardiac hypertrophy is a homeostatic response to elevated afterload. Na+/H+ exchanger (NHE) inhibition reduces the hypertrophic response in animal models of left ventricular hypertrophy (LVH) and myocardial infarction. We examined the effect of chronic treatment with cariporide, a selective inhibitor of Na+/H+ exchanger isoform 1 (NHE-1), on left ventricular (LV) systolic and diastolic function under pressure overload conditions.

Video-assisted orotracheal intubation in mice.

Orotracheal intubation in mice is a complicated technique because of the peculiar oropharyngeal anatomy and the difficulty in visualizing the laryngis aditus. Here we report a new and simple method for rapid endotracheal intubation by using a small bore, straight fibre-optic arthroscope. Under endoscope-assisted visualization of the laryngis aditus, a polyethylene cannula, inserted on a guide-wire in order to facilitate the introduction of the tip across the vocal cords, was advanced in the trachea.

Inhibition of left ventricular remodelling preserves chamber systolic function in pressure-overloaded mice.

Controversy exists whether the development of left-ventricular hypertrophy (LVH) is a mechanism able to prevent cardiac dysfunction under conditions of pressure overload. In the present study we re-assessed the long-term effects of attenuating LVH by using L- and D-propranolol, which are equally able to inhibit the development of LVH induced by aortic banding. The aortic arch was banded proximal to the left common carotid artery in 71 CD-1 mice that were then assigned randomly to receive L-propranolol, D-propranolol (both 80 mg/kg per day) or vehicle.

Attenuation of aortic banding-induced cardiac hypertrophy by propranolol is independent of beta-adrenoceptor blockade.

Objective: Racemic propranolol attenuates cardiac hypertrophy secondary to abdominal aortic banding-induced pressure overload by a mechanism independent of its effect on cardiac work load. This was only observed, however, using doses of propranolol that were much higher than those needed to induce beta-adrenoceptor blockade. Thus, the question remains as to whether the antihypertrophic effect of propranolol depends on its ability to antagonize cardiac beta-adrenoceptor-mediated action (positive chronotropic effect, trophic effect) or on beta-adrenoceptor-independent action.

Protection by shear stress from collar-induced intimal thickening: role of nitric oxide.

Nitric oxide (NO) has potent relaxant and antiproliferative effects on vascular smooth muscle cells, which may represent an important antiatherosclerotic mechanism. Since one of the major stimuli for NO release is flow-related shear stress, we have investigated (1) the effect of increased shear stress on neointimal formation induced in the rabbit carotid artery by enclosing the vessel in a nonconstrictive silicone soft collar and (2) the role of NO in the antiproliferative effect of increased shear stress. Forty-three New Zealand White rabbits were used.

Endothelin and mechanical properties of the carotid artery in Wistar-Kyoto and spontaneously hypertensive rats.

The aim of this study is to evaluate the role of endothelin in the control of the static mechanical properties of in vitro carotid arteries from 14-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). An in vitro preparation in which the artery was allowed to longitudinally elongate similarly to the in situ carotid artery was employed. The diameter of in vitro carotid arteries subjected to static pressures (from 25 to 200 mmHg in 25 mmHg steps) was determined by videomicroscopy and computer-assisted image analysis, the cross-sectional compliance- and distensibility-pressure curves being then derived.

Effects of cholinergic drugs on neocortical EEG and flash-visual evoked potentials in the mouse.

The effects of single intraperitoneal injection of two cholinesterase inhibitors, physostigmine (PHY; 0.01, 0.025, 0.

ET(A)/ET(B) receptor antagonist bosentan inhibits neointimal development in collared carotid arteries of rabbits.

The contribution of endothelin to the genesis of neointimal development in collared rabbit carotid arteries, a widely accepted model of atherosclerosis, was investigated. Three sets of rabbits were studied. In the first group, a non-occlusive, biologically inert silastic collar was positioned around the right carotid artery of the rabbit.

Effects of low doses of physostigmine on avoidance learning and EEG in two strains of mice.

The effects of the cholinomimetic drug, physostigmine (0, 0.01, 0.025, 0.

Relay activity of 17-beta oestradiol and diethylstilbestrol in a mouse-rat system.

The biological activities of diethylstibestrol (DES) of 17 beta-oestradiol (17 beta E) were initially tested, based on the uterus enlargement induced by different doses given with food to immature female mice. In a second series of experiments, the drugs were given in higher doses per os to rats (relay animals) and after 24 h, the livers of the relay rats were removed. Parts of the livers were freeze-dried and were added (10% w/w) to the food of immature female mice, while the remainder underwent chemical analysis to determine the DES and 17 beta E content.

Ultradian rhythms in the N1-P2 amplitude of the visual evoked potential in two inbred strains of mice: DBA/2J and C57BL/6.

Ultradian rhythmicity has been showed in many behavioural parameters in animals as well as in humans. We investigated the existence of a Basic Rest-Activity Cycle (BRAC) rhythm in amplitude fluctuations of mice's visual evoked potential (VEP) primary component. Two inbred strains of mice, C57BL/6 and DBA/2J, were used to verify the influence of genetics on biological rhythm as well.

Dexamethasone and hormones related to the hypothalamic-pituitary-adrenal axis modulate inherited neocortical spindling in DBA/2J mice.

The role of dexamethasone and hormones related to the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) in the control of the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electrocorticogram (ECoG) of DBA/2J mice was investigated. Both dexamethasone and hormones related to the HPA axis consistently reduced the S&W in DBA/2J mice. Cycloheximide (a protein synthesis inhibitor) pretreatment significantly delayed the reducing effect of dexamethasone on the S&W in mice.

Effects of oxiracetam, physostigmine, and their combination on active and passive avoidance learning in mice.

The nootropic drug oxiracetam (50 and 100 mg/kg) had no effect on one-trial passive avoidance acquisition in CD-1 mice, while the acetylcholinesterase inhibitor physostigmine improved passive avoidance performance at doses of 0.025 and 0.05 mg/kg given either pre- or posttraining.

Opioids and corticosteroids involvement in the regulation of the neocortical spindling episodes in DBA/2J mice.

The present study examined the effects of dexamethasone and RU-38486 on the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electroencephalogram (EEG) of DBA/2J mice. Our data indicated that dexamethasone (1-10-100 micrograms/kg, ip) in a time- and dose-related manner significantly reduce the S&W occurrence in freely-moving DBA/2J mice. Cycloheximide (10 mg/kg, ip), a protein synthesis inhibitor, by itself did not modify significantly the S&W occurrence in mice, but when injected two hours before DEX (100 mg/kg, ip), induced consistent delay of DEX effects.

An EEG analysis of drug effects after mild head injury in mice.

An electroencephalographic (EEG) and behavioral model of head injury in unanesthetized, free moving mice has been used to test the effects of TRH and GM1. In our experimental conditions a mechanical head injury capable of inducing loss of righting reflex for 2 to 60 sec, also induces a consistent decrease of the total power of the spectrum of EEG and a decrease of the power of fast beta band (20-40 Hz) for at least 120 min. TRH, injected after trauma in dose of 10 mg/kg, caused improvement of EEG total power of the spectrum.

MIF-1 can accelerate neuromotor, EEG and behavioral development in mice.

Newborn mice were injected SC daily with 1 mg/kg of MIF-1 or saline during the first 19 days of life. The progress of each pup was monitored for physical (body weight, eye and ear opening), neurobehavioral (reflexes) and neurophysiological (EEG) development until the weaning stage. In early adulthood (40 days of age) mice were tested on a maze learning task.

Naloxone and propranolol inhibit the disruption of the hippocampal theta waves induced by D-lysergic acid diethylamide in the rabbit.

In the rabbit, naloxone and propranolol antagonize the disruption of the hippocampal theta waves induced by LSD. These results are discussed in view of the reported effects of these drugs in curing hallucinatory symptoms in mentally disturbed patients.

Experimental aluminium encephalopathy: quantitative EEG analysis of aluminium bioavailability.

Single oral doses of aluminium hydroxide (50 to 200 mg/kg) were found to induce in mice a dose-dependent diminution of the power of the 7.5 to 12 Hz frequency band, with a parallel dose-dependent increase of aluminium content in the brain, as early as 45 min after administration, and indicated that aluminium hydroxide is readily absorbed through an empty stomach or duodenum and is able to induce alterations of background EEG rhythms at doses equivalent to the ones used in human therapy. These data suggest that the EEG disturbances of the background type, (which are observed during the early stage of dialysis encephalopathy in man), may be partly due to a pharmacological and therefore reversible effect induced by an increase in aluminium level in the brain.