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Biomedical subjects

R E Tessel

Publications and source records attributed to R E Tessel.

At least 19 recordsLinked to original sources
PubMed1991

Age-dependent hyperresponsiveness of spontaneously hypertensive rats to the pressor effects of intravenous neuropeptide Y (NPY): role of mode of peptide administration and plasma NPY-like immunoreactivity.

The effects of various doses of intravenously (i.v.) infused (5-min duration, 0.1-3.2 nmol/kg/min) or bolus-injected (0.1-3.2 nmol/kg) porcine and/or rat/human neuropeptide Y (NPY) on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of porcine NPY-like immunoreactivity (pNPYir) were examined in conscious, unrestrained spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats of various ages. When administered as an infusion to 12- to 17-week-old SHR, WKY, and SD rats, porcine NPY (pNPY) was more potent in increasing MAP in SHR than in either WKY or SD rats. Infusions of rat/human NPY instead of pNPY resulted in similar increases in potency in 12- to 17-week-old SHR as compared with WKY. This potency-associated hyperresponsiveness to infused pNPY was also observed when 36- to 41-week-old and 6-week-old SHR and WKY were examined, but infused NPY induced similar HR reductions in age-matched rats regardless of rat strain. Furthermore, doses of infused pNPY that elicited significantly greater pressor responses in SHR and WKY (0.32 nmol/kg/min in 12- to 17-week-old rats and 1.0 nmol/kg/min in 6-week-old rats) resulted in essentially identical plasma pNPYir concentrations in the two rat strains. In contrast, hyperresponsiveness to the MAP effects of bolus injections of pNPY in 12- to 17-week-old SHR was manifested as an increase in efficacy rather than potency, was associated with significantly smaller reductions in HR in SHR than in WKY and occurred at plasma pNPYir concentrations that were significantly larger than those required for infusion-associated hyperresponsiveness. These results are consistent with the hypothesis that NPY is an important contributor to the development and maintenance of essential hypertension.

Aging↗
PubMed1989

Antagonism of methoxyflurane-induced anesthesia in rats by benzodiazepine inverse agonists.

Injection of the partial benzodiazepine inverse agonist Ro15-4513 (1-32 mg/kg i.p.) or nonconvulsant i.v. doses of the full benzodiazepine inverse agonist beta-CCE immediately following cessation of exposure of rats to an anesthetic concentration of methoxyflurane significantly antagonized the duration of methoxyflurane anesthesia as measured by recovery of the righting reflex and/or pain sensitivity. This antagonism was inhibited by the benzodiazepine antagonist Ro15-1788 at doses which alone did not alter the duration of methoxyflurane anesthesia. In addition, high-dose Ro15-4513 pretreatment (32 mg/kg) antagonized the induction and duration of methoxyflurane anesthesia but was unable to prevent methoxyflurane anesthesia or affect the induction or duration of anesthesia induced by the dissociative anesthetic ketamine (100 mg/kg). These findings indicate that methoxyflurane anesthesia can be selectively antagonized by the inverse agonistic action of Ro15-4513 and beta-CCE.

Anesthesia↗
PubMed1989

Mechanisms of phenylalanine-induced pressor effects in conscious rats.

Phenylalanine and tyrosine reportedly decrease blood pressure in conscious restrained rats. However, tyrosine has recently been found to increase blood pressure in anesthetized animals, questioning the generality of findings obtained in restrained animals. The present study therefore evaluated the effects of phenylalanine on mean arterial pressure (MAP) and heart rate (HR) in unrestrained, conscious rats. Phenylalanine (0.32-1.33 mmol/kg i.p.) increased MAP and decreased HR, effects that were antagonized by carbidopa and prazosin but not by desipramine. In addition, both DOPA and tyrosine (1.33 mmol/kg) increased MAP. In contrast, phenylalanine-induced increases in plasma concentrations of its indirectly acting sympathomimetic amine metabolite, phenethylamine, were small and temporally unrelated to the phenylalanine-induced MAP elevation, and desipramine inhibited MAP increases produced by exogenous phenethylamine. These observations indicate that phenylalanine increases MAP in conscious, unrestrained animals by augmenting peripheral catecholamine synthesis and release rather than by affecting phenethylamine bioavailability.

Animals↗
PubMed1986

Antagonism of the behavioral effects of cocaine and d-amphetamine by prazosin.

Key pecking by pigeons was maintained under a 30-response fixed-ratio schedule of food delivery; lever pressing by squirrel monkeys was maintained under a 3-min fixed-interval schedule of food delivery. Administered alone, d-amphetamine (0.1-3.0 mg/kg), cocaine (1.0-3.0 mg/kg) and bupropion (1.0-30 mg/kg) either did not affect or decreased fixed-ratio responding of pigeons, whereas d-amphetamine (0.056-0.3 mg/kg) either increased or decreased (0.56 mg/kg) responding of monkeys maintained under the fixed-interval schedule. Prazosin, a selective centrally-active alpha 1 antagonist, produced a dose-dependent reversal of the rate-decreasing effects of d-amphetamine and cocaine but not of bupropion on fixed-ratio responding in pigeons. Prazosin also reversed both the rate-increasing and rate-decreasing effects of d-amphetamine on fixed-interval responding of squirrel monkeys. In contrast, the non-selective alpha-antagonist phentolamine enhanced d-amphetamine-induced decreases in fixed-ratio responding. These findings suggest that the behavioral effects of d-amphetamine and cocaine are produced at least in part by activation of central alpha 1 receptors. Prazosin may be a useful tool for better understanding the mechanisms through which cocaine, amphetamine, and other abused stimulant drugs exert their potent behavioral effects.

Animals↗
PubMed1985

Prazosin: effect on psychomotor-stimulant cues and locomotor activity in mice.

Mice trained to discriminate 1 mg/kg d-amphetamine from saline, or the selective norepinephrine uptake inhibitor, nisoxetine, from saline, cross-generalized to the alternate drug. They also generalized to 5.6 mg/kg cocaine. The cues produced by amphetamine were antagonized by the selective alpha 1-adrenoceptor antagonist, prazosin, and slightly potentiated by the selective alpha 2-adrenoceptor antagonist, yohimbine. The nisoxetine cue was also antagonized by prazosin. In contrast, the peripherally acting sympathomimetics, p-hydroxyamphetamine and phenylpropranolamine, failed to substitute for, and pimozide and propranolol failed to block, either drug cue. In addition, prazosin, at a dose that did not affect either saline-associated locomotor behavior in mice or the locomotor-activity increase produced by the dopamine uptake inhibitor, bupropion, also antagonized the locomotor stimulation produced by amphetamine and cocaine. Thus, in mice, both the cues and locomotor stimulation produced by amphetamine and cocaine appear to be at least partially mediated by central alpha 1-adrenoceptor activation secondary to increased central synaptic concentrations of norepinephrine.

Amphetamine↗
PubMed1985

Cold-restraint stress and urinary endogenous beta-phenylethylamine excretion in rats.

Stress applied to humans increases the urinary excretion of the endogenous amphetamine-like substance beta-phenylethylamine (PEA), a potentially common mediator of amphetamine and stress effects. The present study was conducted to determine if cold-restraint stress in the rat could represent an animal model for stress-induced changes in PEA disposition in humans. The stressor markedly elevated the urinary excretion of endogenous PEA in a manner that was not attributable to changes in urinary pH, glomerular filtration rate or in food consumption. In addition, a large diurnal variation in PEA excretion was noted. The data suggest that the variables responsible for stress-induced alterations in endogenous PEA disposition in humans and rats are generally similar. However, they also indicate that in rats, in contrast to humans, PEA disposition is subject to diurnal changes.

Animals↗
PubMed1985

Effects of ovarian hormones on the concentrations of immunoreactive neuropeptide Y in discrete brain regions of the female rat: correlation with serum luteinizing hormone (LH) and median eminence LH-releasing hormone.

Recent pharmacological studies have suggested a role for neuropeptide Y (NPY) in control of LH secretion. The present study examined the effects of estradiol benzoate (EB) given alone or in combination with progesterone (P), on the concentrations of immunoreactive NPY in microdissected nuclei of the rat brain, in association with changes in LHRH concentrations and LH release. Forty-eight hours after the administration of EB to ovariectomized rats, serum LH was significantly reduced. Concentrations of NPY, measured by a sensitive and specific RIA, were also reduced in the median eminence, arcuate nucleus, and interstitial nucleus of the stria terminalis. As expected, administration of P to these EB-primed rats induced a sequential rise and fall of LHRH in the median eminence, followed by a marked LH surge in the afternoon. Interestingly, NPY concentrations in the median eminence also increased and then decreased after P, with a time course similar to that shown by LHRH. In the arcuate nucleus and interstitial nucleus of the stria terminalis, P treatment did not affect NPY concentrations further. Sequential EB plus P treatment significantly reduced NPY levels in the medial preoptic nucleus compared to oil vehicle controls. Levels of immunoreactive NPY in the ventromedial nucleus and periventricular nucleus were largely unaffected by ovarian hormone treatments. These results indicate that ovarian steroids, which modulate LH secretion, affect NPY concentrations in those specific areas of the brain which are known to be innervated by the LHRH neurons. These observations support the hypothesis that NPY may participate in the neural regulation of LHRH and LH secretion.

Animals↗
PubMed1984

Inhibitors of phenylethanolamine-N-methyltransferase: effects on brain catecholamine content and blood pressure in DOCA-salt hypertensive rats.

Inhibitors [2-cyclooctyl-2-hydroxyethylamine (CONH), 1 aminomethylcycloundecanol (CUNH), 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF64139), 2,3-dichloro-alpha-methylbenzylamine (DCMB), 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine(LY134046)] of phenylethanolamine N-methyltransferase (PNMT) were found to reduce blood pressure in deoxycorticosterone-salt (DOCA-salt) hypertensive rats. CONH, CUNH and DCMB, but not SKF64139 and LY134046, also lowered blood pressure in normotensive control rats. All of the PNMT inhibitors tested lowered hypothalamic epinephrine (Epi) content in both DOCA-salt hypertensive and normotensive rats. DCMB, SKF64139 and LY134046 also lowered brainstem Epi in both animal groups. From these data a good correlation could not be made between the blood pressure lowering effects of PNMT inhibitors and their effects on hypothalamic Epi content as had been observed in other animal models of hypertension (e.g. spontaneously hypertensive rats).

Animals↗
PubMed1983

Desipramine-induced increase in efflux of endogenous dopamine from rat hypothalamus in vitro: mechanism and specificity.

In vitro exposure of minced rat hypothalamus to desipramine (DMI) resulted in a significant elevation of the net efflux of endogenous norepinephrine (NE) and dopamine (DA) at a drug concentration as low as 10 nM. The net efflux of epinephrine was increased only by a 1000-fold greater concentration of desipramine. The increase in efflux of DA was not secondary to changes in the efflux of NE since nisoxetine elevated the efflux of NE but not of DA and the removal of calcium from the incubation medium blocked the effect of desipramine on the efflux of DA but not of NE. Elimination of calcium did not alter the "spontaneous" hypothalamic efflux of catecholamine. In contrast, desipramine did not affect the net efflux of either DA or NE from the olfactory tubercle or striatum at concentrations of less than 100 microM. At this concentration, the efflux of DA was significantly increased only in the striatum, while the efflux of NE was reduced in the striatum but increased in the olfactory tubercle. Again, in contrast to the hypothalmus, the removal of calcium from the medium markedly reduced "spontaneous" efflux of catecholamine and the desipramine induced efflux of NE, but not the increase in striatal DA efflux produced by desipramine. The results indicate that marked regional differences exist in brain in the ability of desipramine or calcium removal to alter the efflux of both endogenous DA and NE, and suggest that hypothalamic DA and NE neurons are uniquely sensitive to the effects of desipramine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Nisoxetine and amphetamine share discriminative stimulus properties in mice.

The interaction of amphetamine with noradrenergic neurons could mediate a portion of the drug's discriminative stimulus properties. To test this hypothesis, mice were trained to discriminate 1.0 or 3.2 mg/kg amphetamine, 32 mg/kg of the selective norepinephrine uptake inhibitor, nisoxetine, or 32 mg/kg nisoxetine + 1.0 mg/kg amphetamine from saline. Differential drug- or saline-appropriate responding was determined using a two photocell-beam procedure with beam interruption as the operant. Reinforcement (5-sec access to evaporated milk) was presented on a fixed-ratio 20 (FR-20) schedule. Mice trained to discriminate 1.0 mg/kg amphetamine from saline generalized to nisoxetine (32 mg/kg) alone and to doses of 0.56 mg/kg amphetamine and above but not to lower doses unless pretreated with nisoxetine (20 or 32 mg/kg). Mice trained to discriminate nisoxetine (32 mg/kg) from saline generalized to 0.56, 1.0 and 3.2 mg/kg amphetamine and generalized to all amphetamine doses when pretreated with nisoxetine (32 mg/kg). Mice trained to discriminate the drug combination from saline generalized to nisoxetine (32 mg/kg) alone, and to 3.2 mg/kg amphetamine tested alone, to 0.56 mg/kg of amphetamine or above when the lower dose of nisoxetine (20 mg/kg) was used, and to all test doses of amphetamine with nisoxetine (32 mg/kg) pretreatment. Mice trained to discriminate 3.2 mg/kg amphetamine from saline generalized to no test dose of amphetamine following either saline or nisoxetine (32 mg/kg) pretreatment. Testing with several doses of pentobarbital (1.0, 3.0, 10.0 and 18.0 mg/kg) resulted in saline-appropriate responding regardless of training group.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1982

Excretion of beta-phenethylamine is elevated in humans after profound stress.

The urinary excretion rate of the endogenous, amphetamine-like substance beta-phenethylamine was markedly elevated in human subjects in association with an initial parachuting experience. The increases were delayed in most subjects and were not correlated with changes in urinary pH or creatinine excretion. The data suggest a stress-related role for beta-phenethylamine.

Adolescent↗
PubMed1982

Inhibitors of phenylethanolamine N-methyltransferase. 1. Effects of 2-cycloocytyl-2-hydroxyethylamine on rat brain and adrenal catecholamine content and blood pressure.

Acute administration of 2-cyclooctyl-2-hydroxyethylamine (CONH), a potent phenylethanolamine N-methyltransferase inhibitor, produced time- and dose-related reductions of blood pressure in spontaneously hypertensive rats (SHR). CONH did not affect the blood pressure of age-paired normotensive Wistar-Kyoto rats (WKY), or the heart rate of either animal group. CONH produced dose- and time-related reductions in epinephrine (Epi) levels in the hypothalamus and brainstem of both SHR and WKY. The drug also produced dose- and time-related reductions in hypothalamic and brainstem norepinephrine concentrations and elevations in dopamine and 3,4-dihydroxyphenylacetic acid concentrations in both SHR and WKY. CONH was about equally effective in reducing brain norepinephrine and Epi concentrations in both animal strains, but CONH was more effective in elevating brain dopamine and 3,4-dihydroxyphenylacetic acid concentrations in SHR than in WKY. Subchronic administration (3 days) of CONH produced a dose-related reduction in blood pressure in SHR, but had no affect on blood pressure in WKY. The changes in blood pressure in SHR were accompanied by a dose-related reduction in hypothalamic Epi concentrations, but the drug treatment produced no affect on the concentration of Epi in the brainstem. The results of this study suggest that brain Epi-containing neurons may be directly involved in the regulation of blood pressure or alternatively they may indirectly control cardiovascular function by modulating brain norepinephrine- and/or dopamine-neuronal activity.

Adrenal Glands↗
PubMed1982

Inhibitors of phenylethanolamine-N-methyltransferase. 2. Comparison of nonaromatic analogs of phenylethanolamines, 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF-64139) and 2,3-dichloro-alpha-methylbenzylamine: effects on rat brain and adrenal catecholamine content and blood pressure.

Intraperitoneal injections of the phenylethanolamine N-methyltransferase inhibitors 2-cyclohexyl-2-hydroxyethylamine, 1-aminomethylcycloundecanol, 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline and 2,3-dichloro-alpha-methylbenzylamine all lowered blood pressures in spontaneously hypertensive rats. The drugs did not affect the blood pressures of age-paired normotensive Wistar Kyoto rats or did the drugs alter the heart rates of either animal group. All of the phenylethanolamine N-methyltransferase inhibitors tested lowered hypothalamic epinephrine content which in spontaneously hypertensive rats could be correlated with the reduction in blood pressure. These data support the hypothesis that central nervous system epinephrine may play an important role in the regulation of blood pressure and in the genesis and/or maintenance of hypertension. The results also suggest the hypothesis that the blood pressure lowering effects of phenylethanolamine N-methyltransferase inhibitors may be mediated by their effects on hypothalamic epinephrine content.

Adrenal Glands↗
PubMed1982

Effects of phenylethanolamine N-methyltransferase inhibitors on rat brain catecholamine levels and body temperature.

Inhibitors of phenylethanolamine N-methyltransferase (PNMT) were found to reduce hypothalamic and brainstem epinephrine (Epi) content, as well as the body temperature of male Sprague-Dawley rats. In the drug-treated animals, the time course for reduction of body temperature was better correlated with the reduction in brainstem Epi content than with the reduction in hypothalamic Epi content. These results suggest that brainstem Epi neurons may be directly involved in the regulation of body temperature by activating the heat production center or by preventing heat loss.

Animals↗
PubMed1980

Norepinephrine uptake inhibitors as biochemically and behaviorally selective antagonists of the locomotor stimulation induced by indirectly acting sympathomimetic aminetic amines in mice.

Pretreatment with the selective noradrenergic uptake inhibitors nisoxetine and desipramine antagonized the locomotor stimulant effect of d-amphetamine without reducing the drug's stereotypy-inducing action. A similar antagonism was observed with imipramine but not with fluoxetine, a selective serotonin uptake inhibitor and structural analog of nisoxetine. The order of potency of antagonism was desipramine greater than nisoxetine greater than imipramine. Nisoxetine also selectively reduced the locomotor activity induced by maximally effective doses of cocaine, d-N-ethyl-amphetamine, and methylphenidate, but not that induced by morphine. Biochemically, nisoxetine blocked the selective reduction in cerebral cortical endogenous and 3H-norepinephrine produced by amphetamine with itself significantly altering either measure. These data support the involvement of norepinephrine in the locomotor stimulant action of indirectly acting sympathomimetic amines.

Animals↗