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J P Chalmers

Publications and source records attributed to J P Chalmers.

At least 19 recordsLinked to original sources
PubMed2001

Ongoing trials of angiotensin-converting enzyme inhibition: what they can tell us.

Abundant evidence has accumulated showing that angiotensin converting enzyme (ACE) inhibitors reduce long-term cardiovascular morbidity and mortality rates in patients with heart failure and myocardial infarction. Fewer completed trials have assessed their potential benefits in this regard in hypertensive subjects, but evidence of benefit is beginning to accrue from studies examining patients with hypertension, particularly in the presence of diabetes and after infarction. Ongoing trials of blood pressure (BP) lowering using ACE inhibition fall into three main categories: 1) those comparing ACE inhibitors with older drugs such as diuretics and beta blockers; 2) those examining more aggressive versus less aggressive lowering of BP; and 3) those investigating BP lowering in patients at high risk for a cardiac event. Among those in the last group is the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), which examines the effects of perindopril-based ACE inhibitor therapy in both normotensive and hypertensive patients who have survived a stroke. This trial is particularly important because it serves as a model for studies of BP lowering across a wide range of BP and BP-related conditions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Neurokinin-1 receptors and spinal cord control of blood pressure in spontaneously hypertensive rats.

In this study we examined blood pressure and heart rate responses to intrathecal administration of a synthetic NK1-receptor agonist, H2N-(CH2)4-CO-Phe-Phe-Pro-NmeLeu-Met-NH2 (GR 73,632), in spontaneously hypertensive rats (SHR) and their progenitor strain, the Wistar-Kyoto rat (WKY). Sodium pentobarbitone anaesthetised rats with implanted intrathecal catheters were paralysed (pancuronium dibromide) and artificially ventilated. Injection of GR 73,632 at the T9 spinal level evoked dose-dependent increases in mean arterial pressure (MAP) in WKY and SHR. SHR had a lower MAP response threshold than WKY but increase in response with increasing dose was less in SHR than WKY. Biphasic blood pressure responses at high doses were observed in both strains. Prior administration of the NK1-receptor antagonist (3 aR,7aR)-7,7-diphenyl-2-[1-imino-2(methoxyphenyl)ethyl] perhydroisoindol-4-one (RP 67,580) significantly reduced the pressor response in WKY but not SHR. The depressor response was not attenuated in either strain.

Analgesics↗
PubMed1999

Activation of spinal opioid receptors contributes to hypotension after hemorrhage in conscious rats.

Opioid receptors are activated during severe hemorrhage, resulting in sympathoinhibition and a profound fall in blood pressure. This study examined the location and subtypes of opioid receptors that might contribute to hypotension after hemorrhage. Intrathecal naloxone methiodide (100 nmol) abolished the fall in blood pressure after hemorrhage (1.5% of body wt; mean arterial pressure 122 +/- 8 mmHg after naloxone methiodide vs. 46 +/- 5 mmHg in controls, P < 0. 001). Intracisternal naloxone methiodide was less effective than intrathecal naloxone methiodide, whereas intravenous naloxone methiodide, which does not cross the blood-brain barrier, did not alter the fall in blood pressure after hemorrhage. These results demonstrate that spinal opioid receptors contribute to hypotension after hemorrhage but do not exclude supraspinal effects. In separate experiments, the subtype-specific opioid antagonists ICI-174864 (delta-antagonist), norbinaltorphimine (nor-BNI; kappa-antagonist), and H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; mu-antagonist) were each administered intrathecally to determine the minimum dose that would attenuate hypotension during severe hemorrhage. These antagonists were effective at similar doses (3 nmol for CTOP, 6 nmol for ICI-174864, and 10 nmol for nor-BNI), although the binding affinities of these three different agents for their target receptors varied >1600-fold. Comparisons of the minimum effective doses of these antagonists in relation to their binding affinities provides strong evidence for the participation of delta-receptors in mediating hypotension after hemorrhage. In contrast, the dose at which nor-BNI was effective suggests an effect at delta-receptors but not kappa-receptors. The efficacy of CTOP, albeit at a high dose, also suggests an effect at mu-receptors.

Animals↗
PubMed1998

The pre-Bötzinger complex and phase-spanning neurons in the adult rat.

To characterise respiratory neurons in the pre-Bötzinger complex of adult rats, extracellular recordings were made from 302 respiratory neurons in the ventral respiratory group of sodium pentobarbitone anaesthetised adult rats. Neurons were located 0 to 1.6 mm caudal to the facial nucleus, and ventral to the nucleus ambiguus. The pre-Bötzinger complex comprised expiratory neurons (22%, 22/100), inspiratory neurons (37%, 37/100) and phase-spanning neurons (41%, 41/100). In contrast, 80% (125/157) of Bötzinger neurons were expiratory, and 80% (36/45) of rostral ventral respiratory group neurons were inspiratory. Rostrocaudally, the pre-Bötzinger complex extended about 400 microns, starting at the caudal pole of the nucleus ambiguus compact formation. The pre-Bötzinger complex was also characterised by a predominance of propriobulbar neurons (81%, 13/16). Furthermore, 68% (33/48) of expiratory-inspiratory neurons found were located within the pre-Bötzinger complex. The variety of neuronal subtypes in the pre-Bötzinger complex, including many firing during the expiratory-inspiratory transition is consistent with the hypothesis that this nucleus plays a key role in respiratory rhythm generation in the adult rat.

Action Potentials↗
PubMed1998

GABA- and glutamate-immunoreactive synapses on sympathetic preganglionic neurons projecting to the superior cervical ganglion.

Our previous work suggests that virtually all of the synapses on sympathetic preganglionic neurons projecting to the rat adrenal medulla are immunoreactive for either the inhibitory amino acid, gamma-aminobutyric acid (GABA) or the excitatory amino acid, L-glutamate. To investigate whether or not this is true for other groups of sympathetic preganglionic neurons, and to determine whether or not the proportion of inputs containing each type of amino acid neurotransmitter is the same for different groups of sympathetic preganglionic neurons, we retrogradely labelled rat and rabbit sympathetic preganglionic neurons projecting to the superior cervical ganglion and used post-embedding immunogold on ultrathin sections to localise GABA- and glutamate-immunoreactivity. The cell bodies and dendrites of both rat and rabbit sympathetic preganglionic neurons projecting to the superior cervical ganglion received synapses and direct contacts from nerve fibres immunoreactive for GABA and from nerve fibres immunoreactive for glutamate. In the rat, GABA was present in 48.9% of the inputs to sympathetic preganglionic neurons projecting to the superior cervical ganglion, and glutamate was present in 51.7% of inputs. Double immunogold labelling for glutamate and GABA on the same section, as well as labelling of consecutive serial sections for the two antigens, indicated that GABA and glutamate occur in separate populations of nerve fibres that provide input to rat sympathetic preganglionic neurons projecting to the superior cervical ganglion. We now have shown that GABA or glutamate is present in virtually all of the inputs to sympathetic preganglionic neurons projecting to the superior cervical ganglion and in essentially all of the inputs to sympathetic preganglionic neurons supplying the adrenal medulla. These findings are consistent with the hypothesis that all fast synaptic transmission in central autonomic pathways may be mediated by either excitatory or inhibitory amino acids. Furthermore, we showed a statistically significant difference in the proportion of glutamate-immunoreactive inputs between sympathetic preganglionic neurons projecting to the superior cervical ganglion and sympathoadrenal neurons (data from Llewellyn-Smith et al. [Llewellyn-Smith, I.J., Phend, K.D., Minson, J.B., Pilowsky, P.M., Chalmers, J.P., 1992. Glutamate immunoreactive synapses on retrogradely labelled sympathetic neurons in rat thoracic spinal cord. Brain Res. 581, 67-80]), with preganglionics supplying the adrenal medulla receiving more excitatory inputs than those supplying the superior cervical ganglion. This increased excitatory input to sympathoadrenal neurons may explain the predominant activation of these neurons following baroreceptor unloading.

Animals↗
PubMed1998

Low-dose diuretic and/or dietary sodium restriction when blood pressure is resistant to ACE inhibitor.

AIM: To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (<100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril. DESIGN AND METHODS: Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet. RESULTS: 19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mm Hg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p<0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours. CONCLUSIONS: In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP.

Adolescent↗
PubMed1997

c-fos identifies GABA-synthesizing barosensitive neurons in caudal ventrolateral medulla.

Hypertension in the conscious rat, elicited by i.v. infusion of phenylephrine, evoked expression of the immediate early gene c-fos in discrete groups of brain stem neurons. Fos-immunoreactive neurons were located in the caudal ventrolateral medulla (CVLM); others were located in the nucleus of the tractus solitarius (NTS). Because of their sensitivity to alterations in arterial pressure, these neurons are likely to subserve the arterial baroreceptor reflex. The aim of this study was to identify the brain stem projections and the neurotransmitter content of the barosensitive CVLM neurons using neuronal tracing and immunohistochemistry. Some of the barosensitive CVLM neurons projected directly to the rostral ventrolateral medulla (RVLM), and many contained the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD). Other CVLM neurons, containing markers of glutamate or catecholamine synthesis, were insensitive to baroreceptor stimulation. This study delineates neuronal pathways acting in the arterial baroreceptor reflex and identifies precisely GABA-synthesizing CVLM neurons as the source of inhibitory input to the RVLM.

Animals↗
PubMed1997

Neurokinin-1 receptor-immunoreactive sympathetic preganglionic neurons: target specificity and ultrastructure.

Substance P is involved in cardiovascular control at the spinal cord level, where it acts through neurokinin-1 receptors. In this study we used immunocytochemistry and retrograde tracing to investigate the presence of the neurokinin-1 receptor and its ultrastructural localization in rat sympathetic preganglionic neurons that project to the superior cervical ganglion or the adrenal medulla. Immunofluorescence for the neurokinin-1 receptor outlined the somatic and dendritic surfaces of neurons in autonomic subnuclei of spinal cord segments T1-T12, whereas immunofluorescence for the tracer, cholera toxin B subunit, filled retrogradely labelled cells. There was a significant difference in the proportion of neurokinin-1 receptor-immunoreactive sympathetic preganglionic neurons supplying the superior cervical ganglion and the adrenal medulla. Thirty-eight percent of the neurons that projected to the superior cervical ganglion were immunoreactive for the neurokinin-1 receptor compared to 70% of neurons innervating the adrenal medulla. Of neurons projecting to the superior cervical ganglion, significantly different proportions showed neurokinin-1 receptor immunoreactivity in spinal cord segment T1 (15%) versus segments T2 T6 (45%). At the ultrastructural level, neurokinin-1 receptor staining occurred predominantly on the inner leaflets of the plasma membranes of retrogradely labelled sympathetic preganglionic neurons. Deposits of intracellular label were often observed in dendrites and in the rough endoplasmic reticulum and Golgi apparatus of cell bodies. Neurokinin-1 receptor immunoreactivity was present at many, but not all, synapses as well as at non-synaptic sites, and occurred at synapses with substance P-positive as well as substance P-negative nerve fibres. Only 37% of the substance P synapses occurred on neurokinin-1-immunoreactive neurons in the intermediolateral cell column. These results show that presence of the neurokinin-1 receptor in sympathetic preganglionic neurons is related to their target. The ultrastructural localization of the receptor suggests that sympathetic preganglionic neurons may be affected (i) by substance P released at neurokinin-1 receptor-immunoreactive synapses, (ii) by other tachykinins (e.g., neurokinin A), which co-localize in substance P fibres in the intermediolateral cell column, acting through other neurokinin receptors, and (iii) by substance P that diffuses to neurokinin-1 receptors from distant sites.

Adrenal Medulla↗
PubMed1997

Lacidipine, hydrochlorothiazide and their combination in systolic hypertension in the elderly.

OBJECTIVE: To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension. DESIGN AND METHODS: Nineteen elderly subjects (five men and 14 women, median age 71 years, range 62-79 years) participated in the study, which had a randomized double-blind crossover design. For each subject there were four treatment phases, each of duration 4 weeks. The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day, separately and in combination, and placebo. Doses of each agent could be doubled after 2 weeks in each phase if the patient's goal systolic blood pressure had not been achieved. The numbers of subjects administered the higher dose of each treatment were 13 for placebo, 14 for lacidipine, 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide. RESULTS: End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo, 159/82 mmHg with lacidipine, 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide. Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases. There was no difference between sitting and standing blood pressure for any phase. Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered. Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine. There was no difference in the frequency of adverse effects among any of the phases. CONCLUSIONS: In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine. In combination the effects of these two drugs on blood pressure are additive.

Aged↗
PubMed1996

Altered responsiveness of medullary depressor neurones to L-glutamate and D-serine in SHR rats.

We have investigated the effects of microinjection of L-glutamate, D-serine and glycine into the caudal ventrolateral medulla (CVLM) of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. In SHR the depressor responses to L-glutamate were significantly enhanced compared to WKY rats, while those to the NMDA-glycine site agonists, D-serine and glycine (in the presence of strychnine) were significantly diminished. Depressor responses to NMDA and D-serine could be blocked with 5-fluro-indole-2-carboxylic acid (FICA, an NMDA-glycine site antagonist). In support of our previous findings, the larger responses of NMDA-glutamate site agonists and smaller responses of NMDA-glycine site agonists in SHR, may suggest that SHR have reduced levels of the endogenous glutamate antagonist, kynurenic acid.

Animals↗
PubMed1996

Tachycardia after glutamate injection in rat spinal cord is not blocked by kynurenate or mimicked by metabotropic agonists.

1. We have used microinjections of glutamate, an ionotropic excitatory amino acid receptor antagonist (kynurenate) and selective ionotropic (NMDA and kainate) and metabotropic (1S-3R-ACPD, trans-ACPD and L-AP4) receptor agonists in the thoracic IML of the rat to define the receptors mediating the tachycardia produced by excitatory amino acid antagonists. 2. Injection of glutamate (delta heart rate = 76 +/- 8 beats/min n = 16), NMDA (delta heart rate = 116.5 +/- 5 beats/min n = 6) or kainate (delta heart rate = 92 +/- 22 beats/min n =6 evokes a tachycardia when injected into the thoracic intermediolateral column. Kynurenate blocked the response to NMDA (-2% of initial response) and markedly attenuated the response to kainate (14% of initial response) but did not alter the response to glutamate (106% of initial response). 3. IS-3R-ACPD did not elicit a tachycardia when injected into the thoracic intermediolateral column and neither trans-ACPD nor L-AP4 induced a tachycardia after kynurenate injection into the thoracic intermediolateral column. 4. Thus stimulation of either NMDA or AMPA/kainate receptors elicits tachycardia in rat thoracic spinal cord but glutamate also activates another receptor type to elicit a tachycardia. The lack of a tachycardia when trans-ACPD, 1S-3R-ACPD or L-AP4 were injected into the thoracic spinal cord suggests that the kynurenate resistant tachycardia elicited by glutamate is not mediated by metabotropic receptors. The kynurenate resistant tachycardia elicited by glutamate is not mediated by any of the known excitatory amino acid receptor types.

Aminobutyrates↗
PubMed1996

Endothelin-1 produces heterogeneous regional haemodynamic effects in conscious rabbits.

Blood flow in the renal artery, superior mesenteric artery and infra-renal abdominal aorta of conscious rabbits was measured by Doppler ultrasound. Arterial pressure, heart rate and blood flow responses were assessed following 0.2 and 0.8 nmol/kg intravenous endothelin-1. The effects of the following antagonists on these responses were examined: phentolamine, propranolol, scopolamine, captopril, nifedipine, indomethacin, the V1-vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP and the competitive nitric oxide (NO) synthase inhibitor NG-nitro L-arginine (NOLA). Hindlimb resistance and arterial pressure responded in two phases, initial vasodilatation followed by vasoconstriction. Renal and mesenteric vasoconstriction occurred without initial vasodilatation. Following 0.2 nmol/kg endothelin-1, arterial pressure decreased by 18.5 +/- 0.8 mmHg, then increased by 25.2 +/- 1.7 mmHg (n = 27). Heart rate changed reciprocally. Renal resistance increased by 533 +/- 73% (n = 12). Mesenteric resistance increased by 420 +/- 34%. Hindlimb resistance decreased 54 +/- 2% (n = 12, all P < 0.01) then increased slightly (P < 0.05). All changes were greater at 0.8 nmol/kg, particularly the hindlimb vasoconstriction. The only antagonist to alter significantly these responses was NOLA, which in the hindlimb attenuated the vasodilatation and accentuated the vasoconstriction. We conclude that most of the haemodynamic effects of endothelin-1 are direct, but that NO generated by NO synthase causes part of the hindlimb vasodilatation, and that endothelin-1-induced vasoconstriction is attenuated by release of NO.

Animals↗
PubMed1995

Effect of indomethacin on blood pressure control during treatment with nitrendipine.

This study tested the hypothesis that treatment with a nonsteroidal anti-inflammatory drug will not alter the hypotensive effect of a dihydropyridine calcium channel antagonist. Fifteen essential hypertensives (ages 58-80 years) had a supine diastolic blood pressure (DBP) < 100 mmHg after 4 weeks monotherapy with nitrendipine 5-20 mg twice daily. They entered a double-blind randomised crossover study in which the addition of indomethacin 25 mg three times daily was compared with placebo in treatment phases each of 4 weeks duration. Subjects were seen weekly and measurements in the last 2 weeks of each phase were compared. Supine blood pressure (mean +/- SE) was higher in the indomethacin phase (158 +/- 4/80 +/- 2) than in the placebo phase (154 +/- 4/76 +/- 3) (p < 0.01 for DBP). In 6/15 (40%) of subjects the increase in supine diastolic blood pressure with indomethacin was > 5 mmHg. Plasma urea was also increased in the indomethacin phase: 7.6 +/- 0.6 mmol/l compared with placebo: 6.3 +/- 0.5 mmol/l (p < 0.001). The study has demonstrated that concurrent treatment with the NSAID indomethacin impairs the blood pressure lowering effect of the dihydropyridine calcium channel antagonist nitrendipine. This increase in blood pressure with indomethacin in subjects treated with nitrendipine may represent either an independent pressor effect of indomethacin or a reduced vasodilator prostanoid contribution to the hypotensive effect of nitrendipine. This blood pressure increase may be sufficient to interfere significantly with clinical blood pressure control in some subjects.

Aged↗
PubMed1995

Bulbospinal sympatho-excitatory neurons in the rat caudal raphe.

OBJECTIVES: To explore the rat caudal raphe nuclei for neurons that respond to activation of baroreceptor nerves and that have a spinal axon, and to compare the behavioural properties of barosensitive bulbospinal neurons in the rat caudal raphe with the properties of barosensitive bulbospinal neurons in the rostral ventrolateral medulla. DESIGN: Extracellular unit recordings were obtained from an area extending up to 1.0 mm caudally from the caudal edge of the facial nucleus. Two sites were explored: the rostral ventrolateral medulla and the midline. MATERIALS AND METHODS: Single-unit recordings were made in anaesthetized (75 mg/kg chloral hydrate and 30 mg/kg sodium pentobarbitone then 3-6 mg intravenously as required), immobilized (2 mg pancuronium as required) Sprague-Dawley rats. Central respiratory drive was recorded from phrenic nerve discharge. The barosensitivity of single units was assessed by R-wave triggered histograms and by histograms of their responses to aortic nerve stimulation or to intravenous injection of phenylephrine. Nociceptors were activated by a brief pinch of the tail. RESULTS: Eleven spontaneously active units in the midline that were inhibited by baroreceptor stimulation and had a spinal axon were studied. Respiratory modulation was present and was predominantly inspiratory. Barosensitive neurons in the rostral ventrolateral medulla were activated by nociceptive inputs; midline barosensitive neurons were not. CONCLUSIONS: The behavioural characteristics of midline neurons differ from those of the bulbospinal barosensitive neurons in the rostral ventrolateral medulla, indicating that raphe spinal neurons have different sets of afferent inputs and may subserve to a distinct physiological role. The present paper is the first report of bulbospinal neurons in the rat caudal raphe that are inhibited by activation of arterial baroreceptors.

Adrenergic Fibers↗
PubMed1994

Disinhibition of the rostral ventral medulla increases blood pressure and Fos expression in bulbospinal neurons.

The GABA agonist muscimol, injected into the depressor area of the caudal ventrolateral medulla, increased blood pressure and increased the expression of the immediate early gene c-fos in the rostral ventral medulla (RVM) of the rat. The number of Fos-immunoreactive (Fos-IR) neurons seen in the RVM was increased 3-fold after muscimol compared to Fos-IR after vehicle treatment. In the rostral aspect of the RVM approximately half of the Fos-IR neurons were identified as spinally projecting after the injection of the retrograde tracer cholera toxin B subunit into the upper thoracic spinal cord. These bulbospinal Fos-IR neurons were identified in the lateral aspects of the RVM, in the area where baroreceptor-sensitive neurons have been identified in electrophysiological studies, and also in more medial areas of the RVM. Fos-IR neurons were also identified in the intermediolateral cell column of the thoracic spinal cord after muscimol injection, but were rarely observed in this area after vehicle treatment. This study demonstrates the functional connectivity of the caudal and rostral areas of the medulla oblongata and the spinal cord, supporting the view that the caudal ventrolateral medulla contains neurons that provide a tonic inhibitory control over neurons in the RVM and that, in turn, the spinally projecting neurons in the RVM provide an excitatory input to the spinal cord sympathetic preganglionic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Different types of centrally acting antihypertensives and their targets in the central nervous system.

The central regulation of blood pressure and other cardiovascular parameters may involve the baroreceptor reflex are, including both adrenergic and serotonergic pathways, as well as amino acids, as neurotransmitters. Both adrenergic and serotonergic pathways have been recognized as targets for clinically relevant, centrally acting antihypertensives, such as clonidine, guanfacine, and alpha-methyl-DOPA. The central components of the hybrid drugs urapidil and ketanserin also involve serotonergic pathways and receptors. For urapidil the stimulation of 5-HT1A-receptors is assumed to induce peripheral sympathoinhibition, whereas for ketanserin the central mechanism is unknown in detail. More recently central imidazoline (I1) receptors have been proposed as the major target for the newer antihypertensives rilmenidine and moxonidine. Clonidine, however, is assumed to be mixed I1- and alpha2-receptor agonist. The distinction between central I1- and alpha2-receptors may potentially offer the design of new antihypertensives, acting like clonidine but with fewer side effects. Finally, the amino acid pathways should be considered as potential targets for centrally acting antihypertensives. Experimental compounds on this basis are available but clinical implications appear to be very remote. In the present survey an outline is given of the various pathways, neurotransmitters, and receptors involved in the central regulation of blood pressure. The different types of centrally acting antihypertensives are subsequently discussed on this basis.

Animals↗
PubMed1994

Bulbospinal neuropeptide Y-immunoreactive neurons in the rat: comparison with adrenaline-synthesising neurons.

Immunohistochemistry and retrograde tracing using cholera toxin B subunit colloidal gold (CTB-gold) has been used to identify neurons in the medulla that contain neuropeptide Y and project to the area of the intermediolateral cell column in either the upper (T2-T4) or the lower (T8-T9) thoracic spinal cord. The rostrocaudal distributions of neuropeptide Y neurons and neuropeptide Y/CTB-gold neurons have been compared with the distributions of adrenaline-synthesising, phenylethanolamine N-methyltransferase-containing neurons and phenylethanolamine N-methyltransferase/CTB-gold neurons visualised in adjacent sections. In particular areas of the rostral medulla similarities in the numbers and distributions of neuropeptide Y neurons and phenylethanolamine N-methyltransferase neurons suggested a coexistence of the peptide within the catecholamine neurons. However, at the most rostral levels of the rostral ventral medulla, the large numbers of phenylethanolamine N-methyltransferase neurons were not matched by similar numbers of neuropeptide Y neurons, so that the phenylethanolamine N-methyltransferase neurons in this area could not all contain neuropeptide Y. In the rostral ventral medulla fewer neuropeptide Y/CTB-gold neurons than phenylethanolamine N-methyltransferase/CTB-gold neurons were observed, so that these bulbospinal peptide neurons might define a subset of the phenylethanolamine N-methyltransferase/CTB-gold neurons, accounting for 25% of the total phenylethanolamine N-methyltransferase bulbospinal projection from the rostral ventral medulla. Other neuropeptide Y/CTB-gold neurons in the dorsal medulla are also likely to contain phenylethanolamine N-methyltransferase. Finally, a population of neuropeptide Y/CTB-gold neurons was identified in the caudal ventral medulla, these neurons appear not to contain catecholamine synthesising enzymes.

Animals↗