Biomedical subjects

N S Gantenberg

Publications and source records attributed to N S Gantenberg.

8 recordsLinked to original sources

PubMed1996

alpha-2-Adrenergic activation of proopiomelanocortin-containing neurons in the arcuate nucleus causes opioid-mediated hypotension and bradycardia.

Treatment of rats for 4 days with alpha-methyldopa, 200 mg/kg/day i.p., increases steady state levels of proopiomelanocortin (POMC) mRNA in the mediobasal hypothalamus, as measured by DNA excess solution hybridization. The increase is prevented by parallel treatment with yohimbine, 2 mg/kg/day i.p., but not by naltrexone, 2 mg/kg/day i.p. Treatment with the peripheral vasodilator hydralazine, 2 mg/kg/day, does not affect POMC mRNA levels. In situ hybridization histochemistry with a cRNA probe for POMC indicates that POMC-containing cells are located within the confines of the arcuate nucleus both in control and in alpha-methyldopa-treated rats, and confirms the increase in POMC mRNA in the latter. Microinjection of 2 micrograms of alpha-methylnorepinephrine unilaterally into the arcuate nucleus of urethane-anesthetized rats causes hypotension and bradycardia, which can be inhibited by 200 ng of yohimbine microinjected into the same site, or by 100 ng l-naloxone microinjected into the ipsilateral nucleus tractus solitarii, but not into the arcuate nucleus. These findings are interpreted to indicate that activation of alpha 2-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus causes beta-endorphin release and stimulation of opiate receptors in the NTS, which results in hypotension and bradycardia, and that this mechanism contributes to the hypotensive action of alpha-methyldopa.

Adrenergic alpha-Agonists↗

PubMed1994

Endogenous gamma-aminobutyric acid (GABA) mediates ethanol inhibition of vagally mediated reflex bradycardia elicited from aortic baroreceptors.

We have previously demonstrated that ethanol depresses baroreflex bradycardia by potentiating the similar action of endogenous gamma-aminobutyric acid (GABA) in the medullary dorsal vagal complex. In the present study we examined the relative contribution of the sympathetic vs. the parasympathetic nervous system and aortic vs. carotid sinus baroreceptors in this effect. Depressor baroreflex responses were elicited in urethane-anesthetized male Sprague-Dawley rats by i.v. injection of graded bolus doses of phenylephrine or by electrical stimulation of the aortic nerve at different frequencies. Methyl-atropine (2 mg/kg i.v.) greatly attenuated, and bilateral cervical vagotomy completely eliminated, phenylephrine-induced reflex bradycardia, whereas propranolol (1 mg/kg i.v.) caused a moderate decrease in the reflex bradycardic response. Ethanol (1 g/kg i.v) did not influence the residual reflex bradycardia after methyl-atropine, but significantly decreased the residual reflex bradycardia after propranolol. Aortic nerve stimulation caused frequency-dependent hypotension, which was unaffected by methyl-atropine, and bradycardia, which was eliminated by methyl-atropine. Depletion of endogenous GABA by pretreatment of rats with 3-mercaptopropionate slightly increased the bradycardic response to aortic nerve stimulation and eliminated its susceptibility to inhibition by ethanol. Acute aortic nerve denervation moderately reduced the reflex bradycardic response to phenylephrine, which was no longer sensitive to inhibition by ethanol. These findings suggest that 1) ethanol inhibits baroreflex bradycardia but not hypotension, 2) the effect of ethanol is selective regarding both the afferent (aortic vs. carotid baroreceptors) and efferent limbs of the reflex (vagal vs. sympathetic) and 3) the effect of ethanol is mediated through endogenous GABA, probably at the level of the dorsal brainstem.

Animals↗

PubMed1993

Attenuation of baroreflex changes in cardiac sympathetic efferent activities during acute myocardial ischemia.

Sympathetic efferent activities to the heart during blood pressure changes were investigated in 11 dogs with acute myocardial ischemia. Normalized sympathetic efferent activities recorded in thoracic cardiac nerves decreased or increased as anticipated in response to transient changes in mean arterial pressure (15 to 25 mm Hg with nitroglycerin or phenylephrine, 2 to 8 micrograms/kg, intravenously). A branch of the left circumflex coronary artery was occluded, and the arterial pressure challenges were repeated at 5, 15, and 25 minutes after the occlusion. The control (preocclusion) responses in sympathetic efferent activities to the heart ranged from +/- 2% to 70% (changes relative to steady state normalized at 100%). Reflex sympathetic efferent responses were diminished at 15 and 25 minutes of ischemia. Several sympathetic efferent baroreflex responses during myocardial ischemia were paradoxic. Reflex sympathetic efferent changes were not affected in sham animals. These results indicate that both increases and decreases in cardiac sympathetic efferent activities during baroreflex challenges are attenuated within 15 to 25 minutes of acute coronary artery occlusion. These findings suggest that an abnormal buffering of blood pressure changes during acute myocardial ischemia might lead to autonomic dysfunction that promotes arrhythmogenesis and sudden cardiac death.

Animals↗

PubMed1992

A novel acetylcholine receptor-related peptide blocks canine cardiac ganglia and inhibits the nicotinic receptor of PC-12 cells.

A 13 amino acid peptide from the calf muscle acetylcholine receptor has been previously shown to bind both snake neurotoxins and acetylcholine. In the experiments reported here a modified complementary peptide (cAChR) derived from that acetylcholine receptor peptide was tested for biological activity in a canine heart preparation. It was expected that the modified complementary peptide would exhibit either acetylcholine-like effects or acetylcholine inhibiting effects, since, as a complementary peptide to the receptor, it should resemble acetylcholine. In these studies cAChR was administered via the sinus node artery of dog hearts in intact animals which were anesthetized with pentobarbital, intubated, and prepared with local cardiac electrograms and force gauges. cAChR was also injected directly into thoracic sympathetic ganglia. Both approaches demonstrated cAChR inhibition of neural transmission, cAChR was added to the medium of carbachol stimulated PC-12 cells. In these cells, derived from a rat pheochromocytoma, sodium flux is controlled by neural nicotinic receptors. With or without preincubation cAChR inhibited carbachol stimulation of sodium flux, exhibiting a Ki of approximately 9 x 10(-5) (similar to that of hexamethonium). Thus cAChR appears to be a novel synthetic peptide which interrupts nicotinic cholinergic neural transmission by acting as an antagonist of the neural nicotinic receptor.

Amino Acid Sequence↗

PubMed1992

Enhanced induction of ventricular arrhythmias during sympathetic stimulation before and during coronary artery occlusion.

We used programmed electrical stimulation to examine the arrhythmogenic influence of the sympathetic nervous system before and during coronary artery occlusion. In 29 anesthetized dogs the left and/or right stellate ganglia were stimulated at 2-8 hertz. Program-induced ventricular arrhythmias included single premature ventricular depolarizations, doublets, triplets, ventricular tachycardia and ventricular fibrillation. Both the number of extrastimuli and the duration of coronary occlusion significantly influenced ventricular arrhythmia induction. After pooling the number of extrastimuli, type of artery occluded, and the duration of occlusion, the influences of unilateral and bilateral stellate stimulations were evaluated. The incidence of induced ventricular arrhythmias was 54% during control conditions (prior to sympathetic stimulation). Right stellate stimulation had no influence on arrhythmogenesis, causing ventricular arrhythmia induction in 52% (NS) of the trials. Left stellate stimulation resulted in increased ventricular arrhythmias (68%; P less than 0.05) in response to programmed electrical stimulation. Bilateral stellate stimulation elevated program-induced ventricular arrhythmias (63%; P less than 0.05). The effects of the stellate stimulations on arrhythmia induction were similar during and up to 180 minutes of coronary occlusion. Thus, the arrhythmogenic influence of sympathetic stimulation was present before and during coronary artery occlusion.

Animals↗

PubMed1992

Cocaine-enhanced arrhythmogenesis: neural and nonneural mechanisms.

Cocaine abuse increases the susceptibility to cardiovascular complications and sudden cardiac death in man. We used programmed electrical stimulation of the heart to examine the arrhythmogenic influence of cocaine. Twenty-three pentobarbital-anesthetized adult dogs underwent programmed electrical stimulation using one to four extrastimuli before and during cocaine infusion. Autonomic decentralization was performed prior to the protocol in eight dogs. Induced ventricular arrhythmias included single premature ventricular depolarizations, doublets, triplets, ventricular tachycardia, and ventricular fibrillation. Intravenous cocaine, and subsequent adrenergic and muscarinic receptor blockade, or calcium channel blockade were evaluated for their influence on arrhythmogenesis. The incidence of induced ventricular arrhythmias was significantly elevated following cocaine and was reduced following propranolol and atropine. Verapamil, however, did not reduce the incidence of induced arrhythmias. In addition, cocaine significantly increased arrhythmia induction in decentralized animals, but propranolol, atropine, and phentolamine failed to reduce the proarrhythmic effects of cocaine in these animals. Thus, cocaine has a proarrhythmic effect on the heart with multiple mechanisms. The adrenergic mechanism appears to be a result of neurotransmitter uptake blockade, whereas the likely ionic mechanism is a neurally independent, direct effect on the heart.

Adrenergic beta-Antagonists↗

PubMed1991

Cocaine depresses cardiac sympathetic efferent activity in anesthetized dogs.

Increased use of cocaine has increased the incidence of sudden cardiac death concomitantly, likely due to life-threatening arrhythmias and/or myocardial ischemia. The effects of cocaine on regulation of the heart and circulation by the autonomic nervous system (which is active during arrhythmias and myocardial ischemia) are not fully understood, however. Therefore, we wished to evaluate the influence of intravenous (i.v.) cocaine on spontaneous thoracic cardiac sympathetic efferent nerve activity in anesthetized dogs. In six pentobarbital-anesthetized dogs, blood pressure (BP), heart rate (HR), and two cardiac sympathetic nerves (6 right-sided, 6 left-sided; 3 preganglionic, 9 postganglionic) were simultaneously recorded. Cocaine was infused for 15 min to a total dose of 6 mg/kg. Sympathetic multifiber efferent activities, HR, and BP were recorded continuously throughout the infusion and quantified at 5-min intervals during the infusion and for 45 min after infusion. Neural activities declined sharply to 54.7% of control (p less than 0.01) after only 5 min of infusion. After 15 min of infusion, nerve activity decreased to 39.4% of control (p less than 0.01). Cardiac nerve activity remained depressed (44.9%; p less than 0.01) 45 min after cocaine infusion. Cocaine caused a slight decrease in both HR and BP at 15 min. The rate-pressure product (RPP) decreased significantly during cocaine infusion. Comparable administration of lidocaine (6 mg/kg i.v. in 15 min) failed to influence cardiac sympathetic efferent activities significantly. We conclude that i.v. cocaine significantly depresses spontaneous cardiac sympathetic efferent neural activities in anesthetized dogs.

Animals↗

PubMed1990

A sample computer system for physiological data acquisition and analysis.

This report outlines a sample configuration of a system which records, stores and analyses, graphically and statistically, neurophysiological and cardiovascular recordings during an experiment. The system is composed of sensitive physiological amplifiers, an analog to digital signal conversion board, scientific software, a 80286-based computer with 640 Kb of RAM, and a laser printer. Each component of the system is described along with the specific task(s) it performs.

Analog-Digital Conversion↗