Biomedical subjects

M van den Buuse

Publications and source records attributed to M van den Buuse.

At least 19 recordsLinked to original sources

PubMed2001

Cardiovascular and behavioural responses to psychological stress in spontaneously hypertensive rats: effect of treatment with DSP-4.

We used a model of psychological stress combining exposure to an open-field novel environment, radio-telemetric measurement of blood pressure and heart rate, and behavioural tracking analysis of behavioural parameters. All rats showed significant increases in blood pressure and heart rate for the duration of open-field exposure, with spontaneously hypertensive rats (SHR) showing markedly greater pressor responses and tachycardia when compared to either Wistar-Kyoto (WKY) or Sprague-Dawley rats (SD rats). Behavioural responses in the open-field were unrelated to the magnitude of cardiovascular responses. Open-field exposure on 4 consecutive days induced similar pressor responses and tachycardia on each day. By contrast, behavioural responses were reduced from the second day of open-field exposure. Treatment of SHR and WKY rats with DSP-4, to deplete central noradrenaline levels, did not affect cardiovascular responses in SHR, whereas WKY rats showed a trend towards inhibition. However, in WKY rats, but not SHR, DSP-4 treatment caused a marked reduction in behavioural activity in the open-field. In conclusion, these data show that: (1) SHR display marked cardiovascular hyperreactivity to psychological open-field stress when compared to two normotensive rat strains; (2) unlike behavioural responses, cardiovascular stress responses do not habituate upon repeated stress exposure; and (3) noradrenergic projections from the locus coeruleus do not appear to play a major role in cardiovascular stress responses in SHR or WKY rats, although they may be involved in behavioural responses in WKY rats.

Adrenergic Agents↗

PubMed2001

Blood pressure, heart rate, and behavioral responses to psychological "novelty" stress in freely moving rats.

We developed a new model of psychological "open-field" stress in freely moving rats. Blood pressure and heart rate of the rats were measured by radiotelemetry and behavior analyzed by video tracking software. Open-field exposure induced marked increases in blood pressure and heart rate. Repeated daily exposure induced pressor responses that were slightly higher on Day 4 when compared to Day 1. Pretreatment with the beta1-adrenoceptor antagonist atenolol inhibited the tachycardia whereas the ganglion blocker pentolinium inhibited the pressor response, indicating involvement of the sympathetic nervous system. Pretreatment with diazepam prevented the novelty stress-induced pressor response and reduced the tachycardia. These results show that the psychological stress of exposing rats to an open field induces marked cardiovascular effects that are mediated by sympathetic hyperactivity. This model is unique in that it focuses on psychological stress and allows concomitant measurement of blood pressure, heart rate, and behavior in freely moving rats.

Animals↗

PubMed2000

Quinpirole treatment increases renal sympathetic nerve activity and baroreflex gain in conscious rabbits: a spectral study.

Intravenous administration of 0.3 mg/kg of quinpirole to conscious rabbits that had been pretreated with domperidone caused a marked increase in blood pressure and renal sympathetic nerve activity with a peak at 5-10 min after injection (25% and 3-fold increase, respectively). Spectral analysis of the blood pressure-renal sympathetic nerve activity relationship in the 0.2-0.4 Hz domain showed that baroreflex gain was markedly increased at 5-10 min (4-fold) and at 20-25 min after injection (3.7-fold). These results show that administration of the dopamine D(2)/D(3) receptor agonist quinpirole causes profound and long-lasting changes in the central integration of the sympathetic baroreceptor-vasomotor reflex.

Animals↗

PubMed2000

Endothelin and dopamine release.

Endothelins and endothelin receptors are widespread in the brain. There is increasing evidence that endothelins play a role in brain mechanisms associated with behaviour and neuroendocrine regulation as well as cardiovascular control. We review the evidence for an interaction of endothelin with brain dopaminergic mechanisms. Our work has shown that particularly endothelin-1 and ET(B) receptors are present at significant levels in typical brain dopaminergic regions such as the striatum. Moreover, lesion studies showed that ET(B) receptors are present on dopaminergic neuronal terminals in striatum and studies with local administration of endothelins into the ventral striatum showed that activation of these receptors causes dopamine release, as measured both with in vivo voltammetry and behavioural methods. While several previous studies have focussed on the possible role of very high levels of endothelins in ischemic and pathological mechanisms in the brain, possibly mediated by ET(A) receptors, we propose that physiological levels of these peptides play an important role in normal brain function, at least partly by interacting with dopamine release through ET(B) receptors.

Animals↗

PubMed1999

Brain dopamine D2 receptor mRNA levels are elevated in young spontaneously hypertensive rats.

Levels of brain dopamine D2 receptor expression were compared between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls by quantitative in situ hybridisation, using a complementary RNA probe for D2 receptor mRNA. In SHR which were 6 weeks of age, significantly higher levels of D2 receptor mRNA were found in the caudate-putamen (42%), nucleus accumbens (23%), olfactory tubercle (17%) and substantia nigra (38%) compared to age-matched WKY controls. D2 receptor mRNA levels were also higher in the substantia nigra (27%) of 12-14-week old SHR compared to WKY. The increased levels of dopamine D2 receptor gene expression displayed in young prehypertensive SHR could implicate altered central dopaminergic activity in the pathogenesis of hypertension.

Aging↗

PubMed1998

Autonomic mechanisms in the acute cardiovascular effects of cocaine in conscious rats.

We studied the differential involvement of central dopaminergic activation and autonomic nervous system regulatory mechanisms in the cardiovascular responses to cocaine in conscious rats. Sprague-Dawley rats, Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were instrumented with catheters in the jugular vein and abdominal aorta at least 5 days before the experiment. Intravenous administration of cocaine (0.1-3.0 mg/kg) caused a dose-dependent increase in blood pressure that was biphasic, with a large and rapid increase peaking at 10 s, followed by a mild sustained pressor response. Pressor responses to cocaine were significantly greater in SHR when compared to WKY rats. However, pretreatment with dopamine D1 receptor antagonist SCH 23390 or the D2 receptor antagonist raclopride did not influence the effects of cocaine. Pretreatment with the alpha-adrenoceptor antagonist phentolamine or the ganglion blocker pentolinium blocked the peak response and reversed the more sustained response into a depressor effect. While pretreatment with propranolol alone did not alter the responses to cocaine, in rats pretreated with phentolamine and propranolol neither a pressor response nor a depressor response was observed. In conclusion, cocaine administration caused marked, but short lasting pressor responses that were mediated by sympathetic activation and alpha-adrenoceptor vasoconstriction with little involvement of central dopaminergic mechanisms. The rapid return of blood pressure towards baseline may be mediated by sympathoinhibition and beta-adrenoceptor-mediated vasodilatation, the latter of which being particularly prominent when alpha-adrenoceptor activation was prevented.

Acute-Phase Reaction↗

PubMed1998

Interaction of the dopamine D2 receptor agonist quinpirole with sympathetic vasomotor tone and the central action of rilmenidine in conscious rabbits.

Previous studies in conscious rats have shown that systemic administration of the dopamine D2 receptor agonist quinpirole causes a centrally-mediated increase in blood pressure which is associated with increased plasma levels of noradrenaline and adrenaline. In addition, treatment with quinpirole caused a marked inhibition of the antihypertensive effect of centrally-acting sympatho-inhibitory drugs such as clonidine, rilmenidine and alpha-methyldopa, suggesting an interaction at the level of sympathetic vasomotor tone. The main aim of the present study was investigate in conscious rabbits the effect of quinpirole on renal sympathetic nerve activity. In addition, we studied the effect of pretreatment with quinpirole on responses to additional quinpirole injections or rilmenidine treatment. Quinpirole treatment caused a prolonged dose-dependent increase in blood pressure and heart rate. Additional injection of quinpirole, 30 min after the first treatment, caused a significantly smaller pressor response (7+/-2 vs. 17+/-2 mm Hg). Injection of rilmenidine caused a larger decrease in blood pressure in rabbits which had been pretreated with quinpirole than in controls (-28+/-3 vs. -14+/-3 mm Hg). Total renal sympathetic nerve activity was markedly increased by quinpirole treatment (3.5-fold), an effect which could be attributed to both increased amplitude and increased frequency of the renal nerve signal. After a second injection of quinpirole, 30 min after the first treatment, only total renal sympathetic nerve activity and amplitude were increased and the effects were reduced. These results show marked actions of quinpirole on renal sympathetic nerve activity in conscious rabbits. However, the previously described apparent desensitisation to the antihypertensive effect of rilmenidine could not be observed in rabbits, suggesting marked species differences in the mechanism and site of action of rilmenidine.

Adrenergic alpha-Agonists↗

PubMed1998

Endothelin induces dopamine release from rat striatum via endothelin-B receptors.

The aim of the present study was to determine whether local administration of endothelin induces the release of dopamine in the rat striatum and to characterize and localize endothelin receptors in this brain region. Local injection of endothelin-1 (10 pmol) into the ventral striatum of urethane-anaesthetized rats caused an increase of 8 microM in the extracellular concentration of dopamine as measured by in vivo chronoamperometry. The peak increase in dopamine concentration occurred within 5 min of endothelin injection. Injection of the selective endothelin-B receptor agonist [Ala1.3,11.15]endothelin-1 (10 pmol) also caused an increase in extracellular dopamine concentration, suggesting that endothelin is acting at the endothelin-B receptor to elicit its effect. In rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway, the response to local injection of endothelin-1 (10 pmol) was significantly inhibited on the lesioned side as compared to the non-lesioned side. In contrast, pretreatment of the rats with the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (5 mg/kg, i.p.) or the nitric oxide synthase inhibitor NG-nitro-L-arginine (3 mg/kg, i.p.) did not alter the endothelin-induced release of dopamine. In binding studies, addition of endothelin-1 displaced [125I]endothelin-1 with a Ki of 220 pM. The endothelin-B receptor antagonist BQ788 displaced [125I]endothelin-1 with a Ki of 120 nM, whereas the endothelin-A receptor antagonist BQ123 produced only a 25% displacement at 10 microM, suggesting that endothelin receptors in the striatum are of the endothelin-B subtype. In rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopamine system, [125I]endothelin-1 binding was reduced by 53% in lesioned striatum compared to non-lesioned striatum, with no difference in the Kd. These data provide evidence that endothelin acts on a homogeneous population of endothelin-B receptors within the striatum to cause the release of dopamine and that a significant proportion of these receptors is located on dopaminergic neurons.

Animals↗

PubMed1998

Endothelin interactions with brain dopamine systems.

We examined the interactions of endothelin (ET) with dopaminergic systems in rat brain. Using HPLC and radioimmunoassay, we found that striatum contained the highest levels of predominantly ET-1, whereas highest levels of predominantly ET-3 were found in the pituitary. Dopamine depletion in the striatum did not change the levels of immunoreactive ET, even though we have previously found a decrease in the density of ET receptors. In a comparison of spontaneously hypertensive rats (SHR) with Wistar-Kyoto (WKY) rats, ET levels were lower in cerebellum and medulla, with no difference in striatum or in other brain areas. In conclusion, ET is present in high levels in striatum, but these levels are not affected by dopamine depletion or in SHR.

Animals↗

PubMed1998

Role of the mesolimbic dopamine system in cardiovascular homeostasis. Stimulation of the ventral tegmental area modulates the effect of vasopressin on blood pressure in conscious rats.

1. The possible role of the ventral tegmental area (VTA) and its dopaminergic projections in cardiovascular regulation is reviewed. 2. Our own work has shown that stimulation of the VTA by local microinjection of the substance P analogue DiMe-C7 caused an increase in blood pressure. The mechanism of the pressor response was an interaction of central dopaminergic activation, most likely at the level of the baroreflex, with the circulatory actions of vasopressin. 3. These findings are important for a possible role of the mesolimbic dopamine system in cardiovascular homeostasis. Several studies reviewed here show that neuronal activity of the VTA and its mesolimbic projections is altered by changes in blood pressure, salt and electrolyte balance, stress and food and water intake. 4. The VTA and mesolimbic dopamine system, while playing a widely accepted role in locomotor activity, cognition and reward mechanisms, may also be involved in the integration of sensory and behavioural information with cardiovascular homeostasis.

Animals↗

PubMed1997

24-hour recordings of blood pressure, heart rate and behavioural activity in rabbits by radio-telemetry: effects of feeding and hypertension.

We used radio-telemetry to measure 24-hour rhythms of systolic, diastolic and mean blood pressure, heart rate and behavioural activity in conscious rabbits, which were maintained under normal day/night rhythms and restricted feeding. Over three consecutive days, all variables showed little change between day-period and night-period, except for a pronounced rise in the afternoon, coinciding with the presentation of pellet food. Mean blood pressure increased during this period from baseline values between 78-82 mm Hg to a peak of 89-91 mm Hg. At the same time heart rate rose from baseline values of 147-161 b/min to a peak of 206-234 b/min and behavioural activity scores rose from 11-31 counts/h to a peak of 52-81 counts/h. Changing the time at which pellet food was presented to the rabbits from the early afternoon to the early morning, caused a complete and immediate shift of the peak of blood pressure and heart rate to the morning period. Chronic intravenous infusion of angiotensin II caused a significant increase in blood pressure (24-hour average: 80 +/- 1 vs. 114 +/- 7 mm Hg) but did not alter basal heart rate or behavioural activity. The increase in heart rate and blood pressure seen with food presentation was attenuated with angiotensin II infusion. These data show that in rabbits diurnal changes in blood pressure, heart rate and activity were determined to a large extent by timed feeding. In addition, in rabbits with angiotensin-induced hypertension the food-induced changes in blood pressure and heart rate were blunted.

Angiotensin II↗

PubMed1997

Concomitant up-regulation of proopiomelanocortin and dopamine D2-receptor gene expression in the pituitary intermediate lobe of the spontaneously hypertensive rat.

Alterations in central dopaminergic mechanisms in the Spontaneously Hypertensive Rat (SHR) have been previously implicated in the development of the hypertensive phenotype in this rat strain. We have examined the expression and regulation of the dopamine-responsive gene proopiomelanocortin (POMC) in the neurointermediate lobe (NIL) of the pituitary in both SHR and normotensive Wista Kyoto (WKY) rats. Solution hybridization/nuclease protection analysis showed that adult SHR express POMC mRNA in the NIL at approximately 2-4 times the level seen in normotensive WKY controls, associated with a concomitant 2-fold increase in dopamine D2-receptor (D2-R) mRNA expression. Despite the obvious difference in D2-R gene expression, NIL POMC mRNA in both rat strains was regulated in an identical manner following 4 d in vivo bromocriptine or haloperidol treatment. In contrast, though D2-R mRNA expression in the WKY NIL was significantly up-regulated by D2-R blockade with haloperidol, the elevated levels of D2-R mRNA in the NIL of the hypertensive strain were not altered by D2-R antagonism. Following isolation from all hypothalamic input by 5 d in vitro culture, SHR melanotrophs exhibited a 2-3 fold higher rate of beta EP secretion and POMC mRNA expression than melanotrophs derived from normotensive WKY rats, though beta EP secretion was inhibited in a similar fashion by the D2-R agonist quinpirole in both cultures. The current data demonstrate changes in expression of both POMC and D2-R mRNA in the SHR NIL which may be a consequence of altered dopaminergic input and/or alterations in D2-R regulation in this tissue, possibly enabling other factors in addition to dopamine to maintain the NIL of the SHR in a relatively hyperactive state. Whether or not POMC-derived peptides or other factors secreted from the melanotroph cell play any role in the development or maintenance of hypertension in this strain is yet to be established.

Alternative Splicing↗

PubMed1996

Regional expression of c-fos in rat brain following stimulation of the ventral tegmental area.

This study has investigated the effect of stimulating the region of origin of the mesolimbic dopaminergic system, the ventral tegmental area (VTA), with the substance P analogue DiMe-C7 on the regional expression of c-fos in the rat forebrain. We have previously shown this treatment produced a prolonged increase in blood pressure and heart rate which was mediated by both dopaminergic mechanisms and vasopressin release. Stimulation of the VTA resulted in increased levels of c-Fos immunostaining in several target regions of the mesolimbic dopaminergic system (such as the frontal cortex, olfactory tubercle, islands of Calleja and amygdala), with the notable exception of the nucleus accumbens. A marked increase in c-fos expression was also found in the supraoptic nucleus but not the paraventricular nucleus in the hypothalamus. These results support a role for a number of target areas of the mesolimbic dopaminergic system and vasopressin release in the increase in blood pressure and heart rate produced by stimulation of the VTA.

Animals↗

PubMed1996

Intrastriatal injection of endothelin evokes dopaminergic turning behaviour in rats through activation of the ETB receptor.

Contralateral intrastriatal injection of 0.1 pmol or 1 pmol of endothelin-1 produced ipsilateral turning behaviour in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway. This effect could be abolished by pretreatment with either the endothelin ETA/B receptor antagonist bosentan (1 nmol, intrastriatally) or the dopamine D2 receptor antagonist raclopride (0.1 mg/kg, s.c.) suggesting that endothelin is acting at endothelin receptors to evoke ipsilateral turning behaviour and that this response is mediated by dopamine. Similar ipsilateral turning behaviour was observed upon intrastriatal injection of 1 pmol of endothelin-3 or the specific ETB receptor agonist, [Ala1,3,11,15]endothelin-1 when compared to endothelin-1. Pretreatment with the specific ETB receptor antagonist BQ788 blocked the ipsilateral turning response to intrastriatal injection of endothelin-1 while pretreatment with the specific ETA receptor antagonist BQ123 did not significantly change the response to injection of endothelin-1. This indicates that endothelin-1, which has affinity for both ETA and ETB receptors, is most likely acting at the ETB receptor to elicit its effect. These results suggest that low doses of endothelin may act at ETB receptors to evoke the release of dopamine from the striatum in vivo.

Animals↗

PubMed1996

Prolonged central effects of quinpirole on cardiovascular regulation.

Central cardiovascular effects of the dopamine D2 receptor agonist quinpirole were studied in conscious rats. The i.v. injection of 0.3 mg/kg of quinpirole in spontaneously hypertensive rats (SHR) caused a rapid but short-lasting increase in blood pressure. Heart rate showed little change. Pretreatment with the centrally acting selective dopamine D2 receptor antagonist raclopride, but not the D1 antagonist SCH23390, completely prevented the rise in blood pressure. A second injection of quinpirole, 30 min after the first injection, induced little change in blood pressure, although at 4 or 24 hr after quinpirole treatment, we observed partial and complete recovery of the pressor response, respectively. This pattern of desensitization was similar to that seen after administration of the dopamine D2 receptor agonists N-propylnorapomorphine (0.3 mg/kg) or quinelorane (0.1 mg/kg), and was similar in spontaneously hypertensive rats, Wistar Kyoto and Sprague-Dawley rats. At 30 min after treatment with quinpirole, the hypotension induced by i.v. injection of clonidine (0.01 mg/kg) or of 8-hydroxy-dipropylaminotetralin (0.1 mg/kg) was markedly reduced when compared to that in saline-pretreated spontaneously hypertensive rats, suggesting a prolonged effect of quinpirole at the level of sympathetic regulation. The rapid fall in blood pressure caused by i.v. injection of the ganglion blocker pentolinium (10 mg/kg) was slightly, but significantly enhanced by treatment with quinpirole, which suggests an overall prolonged increase in resting sympathetic vasomotor tone. This would be difficult to reconcile with an inhibition of the action of sympatholytic drugs, unless it is hypothesized that the increase in sympathetic vasomotor tone was differential between different sympathetic beds or different neuronal populations in the brain. This may prohibit any additional pressor responses and, through a central feedback mechanism, may inhibit the action of sympatholytic drugs. No evidence was found for lasting changes in circulating levels of vasopressin, angiotensin or atrial natriuretic factor, nor were there changes in hematocrit. Cardiac sympathetic tone appeared to be enhanced, although vagal tone was normal and no major changes in baroreflex sensitivity were observed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1995

Stimulation of the rat mesolimbic dopaminergic system produces a pressor response which is mediated by dopamine D-1 and D-2 receptor activation and the release of vasopressin.

Treatment with dopamine receptor agonists has been shown to induce centrally mediated effects on cardiovascular regulation. We have investigated the effect on blood pressure and heart rate of stimulating the release of endogenous dopamine in the brain from the mesolimbic/mesocortical (A10) dopaminergic system of conscious Sprague-Dawley rats. Stimulation of the region of origin of the A10 dopaminergic system, the ventral tegmental area (VTA), with local micro-injection of the substance P analogue DiMe-C7, produced a dose-dependent increase in blood pressure and heart rate. The injection of 10 nmol of DiMe-C7 produced a maximum increase in blood pressure of 15-20 mmHg at 10 min following administration and a maximum tachycardia of 70-80 B/min. Intravenous pretreatment with the dopamine D-1 receptor antagonist SCH 23390 (0.1 mg/kg) or the dopamine D-2 receptor antagonist raclopride (0.5 mg/kg) markedly inhibited the pressor response and revealed a bradycardia. Furthermore, the pressor response and tachycardia were completely blocked by pretreatment with the vasopressin V-1 receptor antagonist, Pmp1,O-Me-Tyr2-[Arg8]vasopressin (10 micrograms/kg). Pretreatment with the ganglion blocker, pentolinium (10 mg/kg), had little effect on the blood pressure response, however it attenuated the tachycardia. Micro-injection of 10 nmol of DiMe-C7 into a region 2 mm dorsal to the VTA had little effect on blood pressure yet produced a marked bradycardia. The administration of DiMe-C7 into the region of origin of the nigrostriatal A9 dopaminergic system, the substantia nigra, produced a slight but significant increase in blood pressure with little effect on heart rate. Intracerebroventricular administration of DiMe-C7 also produced a pressor response with a more pronounced tachycardia. The blood pressure responses produced by intranigral or i.c.v. injection of DiMe-C7 were not inhibited by pretreating the rats with raclopride. These results suggest an involvement of the mesolimbic A10 dopaminergic system in the regulation of blood pressure and heart rate through the activation of dopamine D-1 and D-2 receptors and vasopressin release.

Animals↗

PubMed1995

Altered expression of dopamine D2 receptor mRNA splice variants in brain and pituitary of spontaneously hypertensive rats.

Both central and peripheral dopamine (DA) has been shown to play a role in the regulation of blood pressure. Using sensitive nuclease protection analysis, we have compared the expression of DA D-2 receptor (D2-R) mRNA splice variants in brain and pituitary of spontaneously hypertensive rats (SHR) with normotensive Wistar-Kyoto (WKY) controls. Levels of D2-R mRNA were significantly altered in pituitary anterior lobe (AL) and neurointermediate lobe (NIL), and in striatum of SHR, but not in any other brain regions examined. SHR pituitary expressed 50-80% higher levels of D2-R mRNA, coupled with an increase in the relative proportion of the long (D2-L) mRNA variant. In contrast, overall D2-R mRNA expression in SHR striatum was only 75% that of WKY controls, however, the relative proportion of the D2-L splice variant was increased. The present data demonstrate that tissue specific alterations in D2-R mRNA levels and primary transcript splicing exist in the SHR and suggest that these changes may in part mediate differential responsiveness to DA that may be related to the development of hypertension.

Animals↗

PubMed1995

Suppression of haloperidol-induced oral dyskinesias in rats by vigabatrin.

Acute and chronic administration of vigabatrin, a selective inactivator of GABA-T, suppresses haloperidol-induced dyskinesias at low doses without preventing the enhancement of striatal dopamine D2 receptor density or the development of vacuous chewing movements. The long-term administration of vigabatrin does not attenuate its effect. The observations presented in this work support the GABA hypothesis of haloperidol-induced vacuous chewing behavior in rats, and suggest that vigabatrin is an appropriate means to enhance nigral GABAergic activity.

4-Aminobutyrate Transaminase↗