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Biomedical subjects

J A Quest

Publications and source records attributed to J A Quest.

At least 37 records · Page 2Linked to original sources
PubMed1984

Comparative effects of urapidil, prazosin, and clonidine on ligand binding to central nervous system receptors, arterial pressure, and heart rate in experimental animals.

We studied the effects of urapidil, clonidine, and prazosin on ligand binding to central nervous system receptors in rats and on arterial pressure and heart rate in chloralose-anesthetized cats. Ligand binding studies indicated that urapidil had 90 times greater affinity for alpha 1 than for alpha 2 adrenergic receptors. Administration of urapidil (129 micrograms) into the cerebroventricles of cats revealed no effect after lateral ventricle injection, a decrease of 9.7 +/- 3.0 mm Hg after fourth ventricle injection, and an increase of 10.8 +/- 2.2 mm Hg after restriction of the drug in the forebrain ventricles. Clonidine (30 micrograms) produced hypotension and bradycardia after injection into the lateral ventricle. Prazosin was ineffective after cerebroventricular injection. Intravenous administration of 0.22, 0.67, and 2.00 mg/kg urapidil produced dose-dependent decreases in arterial pressure that were associated with blockade of alpha 1 adrenergic receptors. Intravenous administration of prazosin elicited the same response. Clonidine (10 micrograms/kg, intravenously produced an initial increase in arterial pressure that was unaffected by pretreatment with urapidil or prazosin. These results suggest that urapidil produces hypotension by an action on the peripheral vasculature and in the hindbrain. The peripheral effect involves blockade of alpha 1 adrenoceptors.

Animals↗
PubMed1984

Blockade of bicuculline-induced pressor and tachycardic responses by forebrain administration of muscimol.

To determine whether i.v. administered bicuculline acts in the forebrain to increase arterial blood pressure and heart rate, this agent was administered i.v. to chloralose anesthetized cats that had muscimol injected into and restricted to the forebrain ventricles. Bicuculline (0.5 mg/kg i.v.) given alone increased arterial pressure by 56 +/- 8 mm Hg and heart rate by 45 +/- 11 beats/min. Bicuculline given to animals exposed to muscimol exhibited no increase in either of these parameters. Muscimol localized to the forebrain did not alter the pressor response to a non-GABA antagonist agent, strychnine, indicating a specific interaction of the drugs with GABA receptors in the forebrain.

Animals↗
PubMed1984

Two-year inhalation toxicity study of propylene in F344/N rats and B6C3F1 mice.

Chronic toxicity studies of propylene were conducted by exposing groups of 50 F344/N rats and 50 B6C3F1 mice of each sex in chambers to air containing the chemical in concentrations of 5000 and 10,000 ppm, 6 hr per day, 5 days per week, for 103 weeks. Groups of 50 rats and 50 mice of each sex in similar chambers received clean air only on the same schedule and served as controls. Survival and mean body weights of exposed and control male and female rats and mice were similar. In exposed rats, increased incidences of nonneoplastic lesions were observed in the nasal cavity. These consisted of epithelial hyperplasia in female rats exposed to the high concentration, and squamous metaplasia in female rats exposed to both concentrations and in male rats exposed to the low concentration. In addition, inflammatory changes characterized by an influx of lymphocytes, macrophages, and granulocytes into the submucosa and by granulocytes into the lumen occurred in male rats of both exposure groups. There was no evidence of nasal cavity lesions in exposed mice, suggesting a species difference in sensory irritation to propylene. There were no treatment-related increases or decreases in tumor incidence in the exposed groups relative to controls for either rats or mice. These data suggest that inhaled propylene induces signs of nasal cavity toxicity in rats but not in mice, and that the chemical is not carcinogenic to either species at the concentrations tested.

Alkenes↗
PubMed1984

Central nervous system site of action of capsaicin-induced cardiovascular changes in the cat.

The purpose of our study was to identify the central nervous system site(s) of action of capsaicin responsible for producing changes in cardiovascular function. To do this, capsaicin was administered into several cerebroventricular regions of chloralose-anesthetized cats while monitoring arterial blood pressure and heart rate. Administration of capsaicin (1, 3, 10, 30, 100 and 300 micrograms) into the forebrain ventricles with restriction of the drug to these ventricles resulted in no significant changes in arterial pressure or heart rate. In contrast, administration of capsaicin into either the 4th ventricle or the cisterna magna resulted in significant increases in arterial pressure and heart rate. Intravenous administration of these doses produced no consistent effects on these indices of cardiovascular function. Bilateral application of capsaicin (3 ng/side) to a ventral medullary site, i.e., Schlaefke's area, known to be a sensitive site for drug-induced cardiovascular responses, resulted in striking increases in pressure and heart rate. Microinjection of this agent into the nucleus tractus solitarius, however, failed to evoke any changes in pressure and heart rate. These results indicate that the area on the ventral surface of the medulla is extraordinarily sensitive to capsaicin and may serve as the site of capsaicin-induced changes in cardiovascular function.

Animals↗
PubMed1983

Central nervous system site of action for the respiratory depressant effect of diacetylmorphine (heroin) in the cat.

The purpose of our study was to identify central nervous system sites involved in the respiratory depressant effect of drugs that stimulate opioid receptors. Diacetylmorphine (heroin) was administered into several cerebroventricular regions of chloralose-anesthetized cats, while monitoring pulmonary ventilation with a Fleisch pneumotachograph. Administration of heroin (17, 50, 150, and 450 micrograms) into the forebrain ventricles, which was restricted to these ventricles, resulted in no significant respiratory effects. In contrast, administration of heroin into either the fourth ventricle or the cisterna magna resulted in a significant (P less than 0.05) decrease in respiratory minute volume (VE). In the fourth ventricle this was because of a decrease in frequency (f) and in the cisterna magna, to a decrease in tidal volume (VT). Intravenous administration of heroin in the same dose-range produced a decrease in VE, which was primarily due to a decrease in f. Bilateral application of heroin (70 micrograms/side) to each of three ventral medullary surface sites (Mitchell's, Schlaefke's, and Loeschcke's areas) known to influence respiration elicited a decrease in VE only at Mitchell's area. This decrease was due to decreases in f and VT. The role of this site in the action of intravenously administered heroin was tested by topical application of naloxone to this area in animals with respiratory depression evoked by intravenous heroin. Bilateral application of naloxone (15 micrograms/side) to Mitchell's area restored breathing to normal. These results lead us to suggest that the site of heroin-induced respiratory depression is a specific area (Mitchell's area) on the ventral surface of the medulla.

Administration, Topical↗
PubMed1983

Activation of central nervous system cholecystokinin receptors stimulates respiration in the cat.

Cholecystokinin-octapeptide (CCK-OP) was injected into the lateral brain ventricle of chloralose-anesthetized cats while monitoring pulmonary ventilation, mean blood pressure (BP) and heart rate (HR). Initial values for respiratory minute volume, BP and HR were 436 +/- 32 ml/min, 126 +/- 8 mm Hg and 204 +/- 9 beats/min, respectively. CCK-OP in doses of 8.8 x 10(-13) to 8.8 x 10(-10) M (i.e., 1 to 1000 ng) increased respiratory minute volume by +56 +/- 18 ml/min to +370 +/- 73 ml/min, respectively. This response was due to an increase in tidal volume (P less than .05) with no effect on respiratory rate. Most of these doses increased BP and HR (P less than .05). These responses were mimicked when CCK-OP was administered into and restricted to the lateral and 3rd ventricles, whereas no significant responses occurred with administration into the 4th ventricle. The highest dose of CCK-OP, when given i.v., produced no significant effects. Central nervous system injections (lateral ventricle) of CCK-OP in deafferented animals also produced respiratory and cardiovascular stimulation, but higher doses were required. Central nervous system injections of comparable doses of desulfated CCK-OP or pentagastrin had no effect on respiratory minute volume, BP or HR. Proglumide (0.8 and 8.0 mg), a specific CCK receptor antagonist, prevented both respiratory and cardiovascular effects induced by CCK-OP. These doses of proglumide exerted no antagonism of CO2-induced respiratory stimulation. These data suggest that a specific receptor reacting with CCK-OP may be important for the control of respiration.

Animals↗
PubMed1982

Central cardiovascular effects produced by the GABA receptor agonist drug, THIP.

In chloralose-anesthetized cats, injection of THIP (30-1000 microgram) into the fourth ventricle produced dose-dependent decreases in blood pressure and heart rate. Administration of similar doses into either the lateral and third ventricle or administration of the largest dose intravenously did not produce these effects. Microinjection of THIP (1.95 microgram) into nucleus ambiguus reversed bradycardia evoked by microinjection of bicuculline methiodide (160 ng) into this nucleus. These results confirm previous findings indicating that activation of GABA receptors in the hindbrain produces hypotension and bradycardia as well as reversal of bicuculline-induced activation of cardiac parasympathetic nerves.

Animals↗
PubMed1981

Blood pressure and heart rate effects of prostaglandin E2 and F2 alpha produced by intracerebroventricular injections in cats.

Blood pressure and heart rate effects of prostaglandin E2 and F2 alpha were examined after administering each agent into the left lateral brain ventricle of chloralose-anesthetized cats. Administration of prostaglandin E2 (1 micrograms) resulted in significant, prolonged increases in arterial pressure (25.7 +/- 6.7 mm Hg) and heart rate (19.4 +/- 07.7 beats/min). These responses were mimicked when the same dose of prostaglandin E2 was administered into and restricted to the lateral and third ventricles via cannulation of the cerebral aqueduct, whereas no significant cardiovascular responses occurred with administration into the fourth ventricle. Intravenous injection of prostaglandin E2 resulted in a transient decrease in blood pressure but no change in heart rate. Administration of prostaglandin F2 alpha (1 and 3 micrograms) into the CNS produced no significant cardiovascular responses. The same was true when prostaglandin F2 alpha was administered by the intravenous route. These results indicate that pronounced cardiovascular effects can be produced by administering prostaglandin E2 but not F2 alpha into the CNS, and that the central site of action of prostaglandin E2 is in the forebrain.

Animals↗
PubMed1978

Effects of serotonin antagonists on digitalis-induced ventricular arrhythmias.

The present study was performed to determine whether pharmacological blockade of serotonin receptors would counteract digitalis-induced ventricular arrhythmias. The effect of the serotonin receptor blocking drugs, methysergide, cinansersin, and cyproheptadine on ventricular arrhythmias produced by ouabain was studied in anesthetized dogs. Each of the three serotonin receptor blocking drugs given as a bolus i.v. injection of 1.5--3.0 mg/kg produced an antiarrhythmic effect. In addition, methysergide administered in the above doses to cats intoxicated with deslanoside, restored an abnormal ventricular arrhythmia to either sinus or junctional rhythm. Methysergide, administered to cats intoxicated with deslanoside but pretreated with p-chlorophenylalanine, exerted an antiarrhythmic effect in less than half of the animals tested. These data indicate that serotonin antagonists are effective in counteracting digitalis-induced ventricular arrhythmias and support the notion that a serotonergic mechanism may be mediating the arrhythmogenic effect of digitalis.

Animals↗
PubMed1976

Effect of dihydro-ouabain on vascular tone on the perfused cannine hindlimb.

Digitalis compounds are known to cause contraction of vascular smooth muscle. However, it has been reported by Kahn and colleagues (J. Pharmacol. Exp. Ther. 142: 215-222, 1963) that dihydro-ouabain has no effect on vascular tone in dogs. The purpose of our study was to reassess the vasoconstrictor activity of dihydro-ouabain. This was done by monitoring perfusion pressure of the canine hindlimb preparation perfused at a constant rate of blood flow and administering intra-arterial injections of dihydro-ouabain. Increasing doses of this drug (i.e., 25, 50, 100, 200 and 300 mug) produced significant dose-dependent increases in perfusion pressure. Pretreatment with phentolamine prevented the effect of dihydro-ouabain on perfusion pressure. These results indicate that dihydro-ouabain causes contraction of vascular smooth muscle by an adrenergic mechanism.

Animals↗