Clonidine: understanding its disposition, sites and mechanism of action.
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Animals↗
Biomedical subjects
S J Lewis
Publications and source records attributed to S J Lewis.
Angiotensin II receptors and angiotensin converting enzyme in the medulla oblongata.
Quantitative in vitro autoradiography was used to map angiotensin II (ANG II) receptors and angiotensin converting enzyme (ACE) in sections from rat, rabbit, sheep, and human medulla oblongata and to follow changes in receptor and ACE density after disruption of vagal projections by nodose ganglionectomy in the rat. ANG II receptors and ACE are both concentrated in the nucleus of the solitary tract and dorsal motor nucleus of vagus of the rat, rabbit, sheep, and human. An ANG II receptor-containing band connecting the nucleus of the solitary tract with the dorsolateral medulla was seen in rabbit and human tissue, providing evidence for association of ANG II receptors with vagal afferent fibers. ANG II receptors were found to be concentrated in the rostral and caudal ventrolateral medulla, which corresponded to the region of C1 and A1 catecholamine-containing cell groups in the rabbit. This localization was also evident in rat and human tissue. In all four species, a prominent, ANG II receptor-rich band in the intermediate reticular nucleus was found to connect the ventrolateral medulla and the dorsal vagal complex. In humans and sheep, this band contains puncta that overlie cell bodies. One week after nodose ganglionectomy in the rat, the density of ANG II receptors in the ipsilateral dorsal vagal complex fell markedly. This fall was most prominent in the rostral dorsal motor nucleus of vagus (to 46% of control density) and in the nucleus of the solitary tract (to 56% of control). ACE levels and calcitonin gene-related peptide receptor density were unchanged in both nuclei after ganglionectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗
Regional brain concentrations of several putative peptide neurotransmitters in normotensive and spontaneously hypertensive rats: effects of continuous (10-day) clonidine infusion.
In the present study, the mean arterial pressures (MAP) and heart rates (HR) were measured in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) that had received a 10-day continuous subcutaneous infusion of either saline or the centrally acting alpha-adrenoceptor agonist clonidine (10 micrograms/kg/h). In separate groups of similarly treated rats, the concentrations of neurotensin (NT), vasoactive intestinal polypeptide (VIP), cholecystokinin octapeptide (CCK-8), calcitonin gene-related peptide (CGRP), and neuropeptide Y (NPY) were measured in the cortex (COR), hypothalamus (HYP), medulla oblongata/pons (MO/P), and cervical (CSC) and thoracic (TSC) spinal cord. In comparison to the WKY rats, the SHR had significantly lower neuropeptide concentrations within the COR (NPY, CCK-8), HYP (NT), MO/P (NPY, NT, and CCK-8), CSC (all neuropeptides), and TSC (NPY, NT, CCK-8, and VIP). The infusion of clonidine lowered the MAP of the WKY and SHR rats (-10 and -35 mm Hg, as compared with respective saline controls) and HR in the WKY rats (-45 beats/min). In general, the infusion of clonidine produced decreases in neuropeptide levels within the CNS of the WKY rather than the SHR strain. When there was a strain difference (i.e., SHR less than WKY), it was evident, particularly within the spinal cord, that clonidine reduced the levels of the neuropeptides in the WKY rats to those levels in the SHR. These findings suggest that the reduced neuropeptide concentrations of the SHR (particularly those within the CSC) and TSC may be a result of, rather than a causal factor in, hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The Vietnam veteran in the workplace.
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Employment↗
Tolerance to the anticonvulsant effects of clonazepam and clobazam in the amygdaloid kindled rat.
A major problem in the treatment of clinical epilepsy with benzodiazepines is the development of tolerance. This is most marked with the 1,5-benzodiazepine, clobazam, but is also noted with the 1,4-benzodiazepine, clonazepam. This study examined the effects of chronic treatment with clobazam, clonazepam and the non-benzodiazepine sodium valproate on the amygdaloid kindled rat with a view to developing an animal model of tolerance. Twice daily intraperitoneal injections of vehicle (1 mL/kg), clonazepam (0.3 mg/kg), clobazam (4.0-8.0 mg/kg) or sodium valproate (200 mg/kg) were given to fully kindled rats for 12 days, in the case of clonazepam and valproate, and for 16 days for clobazam. All rats were stimulated 30-60 minutes (depending on the drug) after the morning dose. The amygdala after-discharge duration (recorded on the EEG) and the seizure stage were determined. While all three drugs initially blocked the kindled seizure, tolerance developed to clonazepam and clobazam but not to valproate. Statistical analysis of the results showed a significant linear trend in the development of tolerance to clonazepam after day 5, but tolerance to clobazam appeared in a more abrupt manner after day 2. The clobazam group were then given a further 2 days of treatment with clonazepam (0.3-0.6 mg/kg) and this blocked the kindled seizures. The amygdaloid kindled rat is a suitable model for studying tolerance to the anticonvulsant effects of benzodiazepines. Further experiments are currently in progress to examine the effectiveness of change-over therapy between clobazam and clonazepam as a means of overcoming tolerance.
Amygdala↗
Regional brain concentrations of vasoactive intestinal polypeptide in normotensive Wistar-Kyoto and spontaneously hypertensive rats.
The regional brain and spinal cord concentrations of vasoactive intestinal polypeptide immunoreactivity (VIP) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative order of distribution of VIP in the WKY strain was cortex (44 pmol/g) greater than hippocampus = striatum greater than midbrain = hypothalamus greater than medulla oblongata/pons = lumbar spinal cord (SC) greater than cervical SC greater than thoracic SC (2.5 pmol/g) whereas in the SH strain this order was cortex (35 pmol/g) greater than striatum = midbrain greater than hippocampus = hypothalamus greater than medulla oblongata/pons = lumbar SC greater than cervical SC greater than thoracic SC (1 pmol/g). The VIP concentrations of the thalamus, cerebellum and pituitary were at the level of assay sensitivity (0.5 pmol/g) in both strains. In comparison to the WKY, the SH rats had significantly lower VIP levels in the hippocampus (-42%) and cervical (-46%) and thoracic (-56%) spinal cord but significantly higher levels in the midbrain (+64%).
Animals↗
Modification of the circadian body temperature rhythm of the spontaneously hypertensive rat during and following cessation of continuous clonidine infusion.
The effects of continuous clonidine infusion (10 micrograms/kg/h for 10 days) and the cessation of this infusion on the circadian body temperature rhythm of the spontaneously hypertensive (SH) rat were examined. This circadian rhythm was blunted significantly during the infusion of clonidine. The fall in body temperature which normally occurs at the onset of each light phase was attenuated during the clonidine infusion, and as such, these rats displayed a relative hyperthermia over the light but not the dark phases. On cessation of infusion (24:00 h), a distinct hyperthermia occurred within the immediate dark phase and the subsequent light phase. The results demonstrate that the circadian control of body temperature is disturbed both during and after continuous clonidine infusion.
Animals↗
Angiotensin II receptor binding in the rat nucleus tractus solitarii is reduced after unilateral nodose ganglionectomy or vagotomy.
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Angiotensin II↗
The effects of intracerebroventricular administration of compound 48/80 on behaviour and regional brain amine concentrations in the rat.
The intracerebroventricular injection of the mast cell degranulator, compound 48/80 (C48/80, 10 micrograms/kg), produced a marked behavioural syndrome in rats which included head and body shakes, paw tremor, excessive grooming, unusual posture and gait, mild diarrhoea, piloerection, extreme agitation and irritability to touch, sedation and catatonia. Fifteen minutes after C48/80, the histamine concentrations were decreased significantly in all brain regions examined, i.e. the cortex, cerebellum, midbrain, medulla oblongata-pons (MO-P) and hypothalamus. The noradrenaline (NA) concentrations were decreased in the cerebellum, hypothalamus and MO-P, whereas the dopamine (DA) content was decreased in the MO-P only. The concentrations of serotonin were not affected. As such, the behaviours following the acute degranulation of brain mast cells by C48/80 may result predominantly from the release of histamine and possibly NA and DA.
Animals↗
Alcoholism: the illness. The occupational health nurse as a link to survival.
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Alcoholics Anonymous↗
Body temperature during and following 10-day subcutaneous infusion of clonidine in the rat.
Body temperature in the rat was measured during and after cessation of the continuous subcutaneous infusion of clonidine (10 micrograms/kg per hr) for 10 days. The body temperature of control animals displayed a distinct circadian rhythm. On each day the mean body temperature over the dark phase (2000-0800 hr) was consistently higher (0.6-0.9 degrees C) than the following light phase. The infusion of clonidine was essentially devoid of initial effects on body temperature. However, during the light phases of day 2 onwards the mean body temperature of the animals treated with clonidine was consistently higher (0.4-0.6 degrees C) than that of controls. No such differences were observed during the dark phases. It appeared that the infusion of clonidine limited the fall in body temperature which normally occurred at the onset of the light phases and this resulted in the treated rats displaying a relative hyperthermia. On cessation of the infusion of clonidine (at 2400 hr on day 11) a distinct hyperthermia was observed within 2 hr and was sustained for the remainder of the dark phase and subsequent light phase. This post-infusion hyperthermia was more pronounced than that observed during the period of infusion of clonidine. These results demonstrate that the circadian control of body temperature is disturbed both during and after continuous infusion of clonidine.
Adrenergic Fibers↗
Involvement of brain histamine in delta 9-tetrahydrocannabinol tolerance and withdrawal.
The involvement of brain histamine (HA) in delta 9-tetrahydrocannabinol (delta 9-THC) tolerance and dependence was studied in rats. Rats treated for 5 days with delta 9-THC (2-6 mg/kg, IV) developed tolerance to the hypothermic effects of the drug. Tolerance also developed over the 5 day period to the decrease in brain regional HA concentrations observed after an acute injection of delta 9-THC. Administration of the tricyclic antidepressant drug clomipramine hydrochloride to tolerant rats induced a withdrawal-like behavioural syndrome. Accompanying this behaviour was a fall in HA concentrations of the midbrain, cortex, medulla oblongata/pons and the cerebellum. Administration of delta 9-THC, but not of the delta 9-THC vehicle, prior to clomipramine challenge attenuated both the intensity of the withdrawal-like syndrome and the reductions in brain regional HA concentration.
Animals↗
Neurofibromatosis: a familial and family disorder.
Neurofibromatosis (NF) is a devastating illness which is extremely variable in its symptoms, intensity, and progression. Nursing literature has suffered markedly from lack of information on this important health care problem. This article is the result of an interface of the senior author's own personal experience with neurofibromatosis and an extensive review of international and multidisciplinary publications on the subject. The nurse can exert a profound impact on the care of the patient/family experiencing the crisis of neurofibromatosis.
Counseling↗
Attenuation of antigen-induced bronchospasm by fenoterol in the guinea-pig.
When guinea-pigs sensitized to ovalbumin were challenged with ovalbumin, the histamine concentrations in lung tissue decreased, whereas those in tracheal and heart tissues increased during the 15 min following challenge. Fenoterol (2.5 mg/kg, i.p.), administered 30 min prior to challenge, attenuated both the decrease and the increase in lung and tracheal histamine concentrations, respectively. The challenge-induced increase in heart histamine was also prevented. In the anaesthetized guinea-pig, a marked increase in intratracheal pressure (ITP) occurred on challenge. This was of longer latency than the increase in ITP induced by histamine and was consistent with a release process. Treatment of challenged guinea-pigs with fenoterol (2.5 mg/kg, i.v.) markedly reduced the increased ITP. However, when fenoterol was administered prior to challenge, the increase in ITP was abolished. These results indicate that there is an apparent relationship between the inhibition of histamine release in vivo by fenoterol pretreatment and the greater inhibitory effect of fenoterol on antigen-induced increases in ITP when administered prophylactically.
Airway Resistance↗
The development of a relative hyperthermia during continuous clonidine infusion in the rat.
In rats the continuous infusion of clonidine (10 micrograms kg-1 h-1) produces a relative hyperthermia of approximately 0.6 degree C during the light phases but not the dark phases of a 10 day infusion period. It appears that the relative hyperthermia results from a clonidine infusion-induced attenuation of the fall in body temperature which normally occurs at the onset of the light phases.
Animals↗
Rapid eye movement (REM)-sleep during and after continuous infusion of the oxazoline derivate S3341: a comparison with clonidine.
The frequency and duration of rapid eye movement (REM)-sleep episodes were examined in normotensive rats during and after cessation of continuous infusion of either clonidine (10 micrograms/kg/h) or the oxazoline derivative S3341 (50 micrograms/kg/h) for 10 days. Both compounds abolished REM-sleep during the infusion. On cessation of the clonidine infusion there was a rebound increase in the frequency and duration of REM-sleep episodes. These episodes were associated with markedly exaggerated blood pressure fluctuations. On cessation of the S3341 infusion, the frequency and duration of REM-sleep episodes returned to control levels. Blood pressure responses were not different from controls. These post-infusion differences may be related to the greater degree of selectivity of S3341 for the alpha 2-adrenoceptor rather than the alpha 1-adrenoceptor subtype.
Animals↗
Clinical and pathological observations concerning the aetiology of primary lens luxation in the dog.
A series of 123 consecutive referred cases of lens dislocation in the dog were classified as primary (100), secondary (21) and congenital (two). Cases designated as primary lens luxation comprised only the terrier breeds or crossbreds and collectively appeared to represent a single clinical entity characterised by age of onset (mean four to five years), essential bilaterality and the apparent absence of antecedent ocular disease. Elevated intraocular pressures were encountered in many eyes exhibiting subluxation. However, in three Tibetan terriers, on which tonometry was performed on a daily basis for approximately one year during the period of subluxation and before the development of luxation, there was no evidence of abnormal intraocular pressure change, suggesting that ocular hypertension in primary lens luxation is a secondary and not a primary development. All but one of nine affected eyes representing three terrier breeds showed abnormalities of the suspensory apparatus of the lens (zonule) which resembled those reported previously in Tibetan terriers bred for the condition.
Animals↗