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B Jarrott

Publications and source records attributed to B Jarrott.

At least 109 records · Page 6Linked to original sources
PubMed1987

Strain differences in central nervous system neurotensin content between normotensive and spontaneously hypertensive rats.

Regional brain concentrations of neurotensin (NT) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative distribution of NT was similar in the two strains with the hypothalamus having the highest concentration (55-75 pmol/g) and the cerebellum the lowest (3-6 pmol/g). In comparison to the WKY rats, the SH rats had significantly lower NT levels in the hypothalamus (-17%), medulla oblongata-pons (-18%), pituitary (-52%) and spinal cord (-44%). In view of the putative role of NT as a neurotransmitter and its cardiovascular effects following central and peripheral administration, the reduced levels of this peptide may be of importance in the higher blood pressure of the SH rat.

Animals↗
PubMed1987

The current status of monoamine oxidase and its inhibitors.

The enzyme monoamine oxidase (MAO) plays an important role in the inactivation of both dietary amines and also of neurotransmitter amines. A study of the properties of irreversible inhibitors of this enzyme suggests that the enzyme exists in two broad types--MAO-A and MAO-B. Although irreversible inhibitors of MAO were once widely used as antidepressant agents, they fell from favour because of adverse reactions after the ingestion of amine-containing foodstuffs ("the cheese reaction"). However, these inhibitors (phenelzine and tranylcypromine) are probably best for the treatment of atypical depression providing the patient is aware of dietary reactions. A new series of reversible, MAO-A selective inhibitors are being developed which do not exhibit serious dietary interactions. These reversible inhibitors show promise as rapidly acting antidepressant agents. An atypical irreversible MAO-B selective inhibitor, selegiline (deprenyl) does not exhibit an adverse reaction on the ingestion of amine-containing foods. This drug has been used as an adjuvant in the treatment of Parkinson's disease since it allows the dose of L-dopa to be reduced by approximately 25%. More important, selegiline may slow the degeneration of dopaminergic neurons that is characteristic of Parkinson's disease.

Allylamine↗
PubMed1987

The pharmacokinetics of captopril and captopril disulfide conjugates in uraemic patients on maintenance dialysis: comparison with patients with normal renal function.

We have measured the plasma concentrations of captopril and total disulfide conjugates of captopril after a 50 mg oral dose in 6 uraemic patients on maintenance dialysis and in 8 hypertensive subjects with normal renal function. The mean peak plasma concentration of captopril was 2.5 times higher (0.447 micrograms X ml-1 vs 0.181 micrograms X ml-1) and the concentrations of the disulfides 4 times higher (3.62 micrograms X ml-1 vs 0.924 micrograms X ml-1) in the uraemic patients. Moreover captopril disulfide conjugates in the uraemic subjects reached peak concentrations at 8 h after the dose and subsequently felt. The apparent plasma half-time was 46 +/- 19 h. Only 15% of these conjugates were removed by dialysis. This marked accumulation of captopril conjugates was associated with a sustained fall in both systolic and diastolic blood pressures. In uraemic patients the mean maximum reduction in systolic and diastolic blood pressures were 37 +/- 7 mmHg and 24 +/- 9 mmHg respectively, occurring 6 h after the dose, compared with 8 +/- 7 and 8 +/- 1 mmHg respectively at 30 min in normal renal function patients. These results are consistent with the results of animal experiments, which show that captopril disulfides can be converted back to free captopril and can contribute to the antihypertensive effect of the drug. They provide a reationale for reducing the dose and frequency of administration of captopril in patients with significant renal impairment.

Adult↗
PubMed1987

Microcomputer analysis techniques for evaluation of benzodiazepine effects on rat electrocorticogram.

Quantitative analysis of drug effects on the EEG is usually performed on a minicomputer using an EEG signal that has been recorded on a high frequency FM tape recorder and edited to remove artefact. However, this equipment is expensive and so the present study evaluated a much cheaper system, an 'on-line' microcomputer and 3 programs for data reduction. Using this system to assess diazepam effects on the rat electrocorticogram, it was concluded that period amplitude analysis may be preferable to the Fast Fourier Transform or Hjorth analysis.

Animals↗
PubMed1987

The development of tolerance to the anticonvulsant effects of clonazepam, but not sodium valproate, in the amygdaloid kindled rat.

The effects of chronic treatment with clonazepam and sodium valproate were studied on kindled amygdaloid seizures in rats. Fully kindled rats were given an intraperitoneal (i.p.) injection of either vehicle (1.0 ml/kg), clonazepam (0.3 mg/kg) or sodium valproate (200 mg/kg) twice daily for 12 days. Each rat was stimulated through an amygdaloid electrode 30 min after the morning dose. While both drugs initially blocked and kindled seizure (P less than 0.01), the results showed a significant trend (P less than 0.02) in the development of tolerance to the anticonvulsant action of clonazepam but no significant tolerance to the action of valproate.

Amygdala↗
PubMed1987

Concentrations of histamine in the hypothalamus of the rat: effect of extraction volume and interpretation of the effects of acutely-administered morphine.

The effect of varying the ratio of extraction volume to tissue weight (EVR) on the apparent concentration of histamine (HA) in the hypothalamus of the rat was examined. Increasing the weight of tissue (by pooling 1, 2 or 3 hypothalami), in a constant extraction volume, resulted in progressive decreases in apparent concentration of histamine in the hypothalamus. These concentrations were 642, 450 and 282 ng/g, respectively. Morphine (10 mg/kg, i.p.) significantly reduced the concentration of histamine in the hypothalamus. Expressed as percentages of the saline-control values (obtained for the extraction volume to tissue weight of 35.7, 57.2 and 118.4 ml/g), treatment with morphine resulted in 24, 17 and 11% reductions in the concentration of histamine in the hypothalamus, respectively. However, expressed in terms of ng/g, the reductions in histamine induced by morphine were 68, 75 and 69 ng/g, respectively. It is concluded that morphine may consistently affect a single pool of histamine. The possibility that de novo histamine is formed in the homogenate during the extraction process is discussed.

Animals↗
PubMed1987

Differential effects of surgical sympathectomy on rat heart concentrations of neuropeptide Y-immunoreactivity and noradrenaline.

The aim of this study was to estimate the proportion of cardiac neuropeptide Y-immunoreactivity (NPY-ir) which is not present in sympathetic neurones innervating the rat heart. The procedure employed was to surgically sympathectomize the heart and then measure the remaining cardiac concentrations of NPY-ir and noradrenaline (NA). Unilateral (left) sympathectomy significantly reduced the levels of NPY-ir and NA in all regions of the heart (by 40-70%) except for the NPY-ir in the right atrium which was unaltered. The effect of bilateral sympathectomy was significantly greater than that of unilateral sympathectomy. Unilateral and bilateral sympathectomy produced similar reductions in the concentrations of NPY-ir and NA in the ventricular tissue. In contrast dissimilar changes were produced in the atrium. Although bilateral sympathectomy almost totally depleted the NA from the right atrium (by 98%), the NPY-ir levels were only reduced by 50%. These results indicate that approximately half the content of NPY in the right atrium is not present in sympathetic noradrenergic neurones. This pool may occur in the previously described intrinsic neurones of the right atrium.

Animals↗
PubMed1987

Rapid eye movement sleep and the associated cardiovascular changes during and after continuous 10-day infusion of clonidine in normotensive rats: comparison with lofexidine and S3341.

The centrally acting alpha-adrenoceptor agonists clonidine, lofexidine, and S3341 vary in their selectivity for the alpha 2-adrenoceptor subtype (S3341 greater than clonidine greater than lofexidine). The aim of this study was to examine the frequency and duration of rapid eye movement (REM) sleep episodes, and the cardiovascular changes associated with these episodes, during and after the continuous (10-day) infusion of saline (0.9% wt/vol), clonidine (10 micrograms/kg/h), lofexidine (10 micrograms/kg/h), or S3341 (50 or 100 micrograms/kg/h) in unrestrained, chronically instrumented rats. During a typical 24-h period, the saline infusion animals (n = 4) had 46 +/- 3 REM sleep episodes of 2.4 +/- 0.1 min duration. The majority of these episodes were associated with relatively minor phasic and tonic changes in arterial blood pressure and heart rate. During infusion, the three drugs markedly reduced the cardiovascular and behavioural signs of REM sleep. On cessation of the clonidine and lofexidine infusions, rebound increases (i.e., to values greater than controls) in the frequency and duration of REM sleep episodes were observed. These episodes were associated with markedly exaggerated fluctuations in arterial blood pressure and heart rate. The REM sleep rebound and associated cardiovascular responses were greater during the post-lofexidine infusion phase. A relatively minor rebound increase in total REM sleep time was observed after cessation of the 100-micrograms/kg/h, but not the 50-micrograms/kg/h, infusion rate of S3341. The cardiovascular responses during the REM sleep episodes were mildly exaggerated after cessation of the higher infusion rate of S3341.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Neurotransmitters and neuropeptides in blood pressure regulation in the spontaneously hypertensive rat.

Studies of the roles played by neurotransmitters in the development of hypertension in the spontaneously hypertensive (SHR) rat are complicated by the presence of genetic differences between SHR and normotensive control rats, which are not related to differences in blood pressure. One approach that may be used in an attempt to overcome this difficulty is to study the manner in which neurotransmitter and metabolite levels change with age, and to relate these changes to alterations in blood pressure with ageing. Noradrenaline (NA) levels in the brainstem and spinal cord of SHR and Wistar Kyoto rats fell with age, while 3,4-dihydroxyphenylethyleneglycol (DHPG) levels (a neuronal metabolite of noradrenaline) remained constant. Similar changes were seen when NA and DHPG levels were measured in the discrete brainstem A1, A2, and C2 region, and when adrenaline, NA, and DHPG levels were examined in the C1 region. Differences in age-related changes of neuropeptide Y (NPY) levels were also found in the ventromedial nucleus of the hypothalamus and the locus coeruleus, and of beta-endorphin in the anterior hypothalamic nucleus, the paragigantocellular nucleus of the brainstem, and the locus coeruleus. These changes may indicate either a progressive increase in the activity of neurons in the sympathoexcitatory C1 region or a progressive reduction in the activity of vasodepressor A1, A2, and C2 regions with ageing, or both. However, changes in catecholamines and metabolites with age were similar in both strains and therefore cannot readily explain the more rapid rise in blood pressure with ageing in SHR rats.

Aging↗
PubMed1987

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↗
PubMed1987

Comparison of pharmacokinetics and pharmacodynamics of adrenoceptor agonists and antagonists as antihypertensive agents.

Central and peripheral alpha-adrenoceptors play an important role in cardiovascular regulation, and selective alpha 1-adrenoceptor antagonists and alpha 2-adrenoceptor agonists have an established place in the therapy of hypertension. Prazosin is a selective alpha 1-antagonist that is both effective in lowering blood pressure and well tolerated. However, the more recently developed alpha 1-antagonists doxazosin and terazosin offer the advantage of having longer half-lives, allowing once daily administration. Clonidine is a centrally acting alpha 2-agonist whose clinical use has often been limited by the dose dependent side effects of dry mouth and sedation, and the belief that it should be given three times per day. However, recent studies have shown that it has substantial antihypertensive efficacy with minimal side effects at low doses, and that half-life is long enough to allow twice daily administration. An improved understanding of the pharmacodynamics and pharmacokinetics of drugs acting on alpha-adrenoceptors allows a more rational approach to their clinical application.

Adrenergic alpha-Agonists↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

Differences between central and peripheral rat alpha-adrenoceptors revealed using binuclear ligands.

We have used two homologous series of binuclear ligands, diacridines and diquinolines, and the radioligand receptor assay to compare the topology of alpha 1- and alpha 2-adrenoceptors in rat cerebral cortex and kidney membranes. While the chain length-dependence of affinity of the diacridines, as well as that of the diquinolines, for the alpha 1-adrenoceptors of these central and peripheral tissues are similar, we find marked differences in affinity profiles for interaction with central and peripheral alpha 2-adrenoceptors. In the context of our previously proposed model for the binding of diacridines and diquinolines to alpha-adrenoceptors the results suggest that the surface features of central and peripheral alpha 2-adrenoceptors differ in the area surrounding the noradrenaline binding site. This difference may prove to be of therapeutic relevance.

Acridines↗
PubMed1986

Comparison of neuropeptide Y immunoreactivity in hypothalamic and brainstem nuclei of young and mature spontaneously hypertensive and normotensive Wistar-Kyoto rats.

The concentration of neuropeptide Y immunoreactivity (NPY-ir) was measured in 8 hypothalamic and 5 brainstem nuclei of 6- and 14-week-old spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Strain differences were observed in 3 hypothalamic nuclei and age-dependent changes occurred in 3 hypothalamic and 2 brainstem nuclei. In both the ventromedial hypothalamic nucleus and locus coeruleus the observed change in NPY-ir with age in SH rats was significantly different to the change observed in the WKY. These strain- and age-related differences in NPY-ir may be of relevance in the development of hypertension in the SH rat.

Age Factors↗