Biomedical subjects

M van den Buuse

Publications and source records attributed to M van den Buuse.

17 recordsLinked to original sources

PubMed1992

Central effects of quinpirole on blood pressure of spontaneously hypertensive rats.

The i.v. administration of the dopamine D-2 receptor agonist quinpirole induced a rapid increase in blood pressure in spontaneously hypertensive rats (SHR). Heart rate showed little change. The pressor response to quinpirole was similar in SHR and normotensive Wistar-Kyoto rats (WKY) at doses of 0.03 to 0.3 mg/kg but, at 1 mg/kg, quinpirole induced a greater increase in blood pressure in SHR than in WKY. In contrast, although both strains showed a decreased locomotor activity after administration of 0.01 to 0.05 mg/kg of quinpirole, only in WKY was activity enhanced by 0.25 to 1.25 mg/kg of quinpirole. The i.v. administration of the dopamine agonists apomorphine, N-propylnorapomorphine and (R)-(+)-3-(3-hydroxyphenyl)-N-propylpiperidine, but not the putative presynaptic D-2 agonist (S)-(-)-3-(3-hydroxyphenyl)-N- propylpiperidine, induced pressor responses in SHR comparable to those after quinpirole administration. The pressor effect of quinpirole was enhanced by pretreatment with the peripheral D-2 antagonist domperidone, but blocked by the centrally acting dopamine antagonists haloperidol or sulpiride. In SHR, which were pretreated centrally with pertussis toxin, quinpirole induced a significantly smaller increase in blood pressure than in control SHR. Pretreatment centrally with 6-hydroxydopamine had no effect on the pressor action of quinpirole in SHR. Thirty minutes after i.v. administration of quinpirole, an additional injection of quinpirole did not significantly change blood pressure. Increasing the interval between two subsequent injections of quinpirole showed that this desensitization slowly reversed, but only after 24 hr had the pressor response to quinpirole fully recovered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Contribution of forebrain noradrenaline innervation to the central circulatory effects of alpha-methyldopa and 6-hydroxydopamine.

We studied the circulatory effects of chronic lesions of the ascending noradrenergic (NA) projections to the forebrain on the acute effects of intracisternal (i.c.) alpha-methyldopa (alpha-MD) and 6-hydroxydopamine (6-OHDA) on mean arterial pressure (MAP) and heart rate (HR) in conscious rabbits with arterial baroreceptors either intact or denervated (sinoaortic denervation, SAD). Both drugs acutely release neurotransmitter from central NA neurons. I.c. 6-OHDA produced acute hypertension and bradycardia while i.c. alpha-MD produced acute hypotension and bradycardia. The responses are qualitatively similar in SAD rabbits except that after 6-OHDA, HR increased. In another group we studied the effects of the drugs 3-4 weeks after localised injections of 6-OHDA in the midbrain dorsal and ventral NA bundles. Local 6-OHDA depleted forebrain regions of NA by 44-76%, and had no effects on basal values of MAP or HR. The pressor and depressor effects, of 6-OHDA and alpha-MD respectively, were little affected by the lesions in either intact or SAD rabbits. By contrast, in rabbits with intact baroreceptors, the lesion abolished the bradycardia produced by i.c. alpha-MD and 6-OHDA. The latter drug now produced a late tachycardia. In SAD rabbits, however, there was no effect on the alpha-MD-induced bradycardia, but the 6-OHDA tachycardia was enhanced. Since the major effects of the lesions were confined to the rabbits with intact baroreceptor afferents, it suggests that the ascending NA pathways are important for the cardiac responses dependent on baroreceptor input. In intact animals, both drugs produce bradycardia through facilitation of the vagal component of the baroreceptor-heart rate reflex. In SAD rabbits, almost all the changes to HR are mediated through the cardiac sympathetic and the lesions have little effect on HR.

Animals↗

PubMed1991

Interaction of bradykinin and angiotensin in the regulation of blood pressure in conscious rats.

1. The interaction between bradykinin (BK) and the renin-angiotensin system was studied in conscious, catheterized rats. 2. Intravenous injection of BK induced dose-dependent decreases in blood pressure in normotensive Wistar and Wistar-Kyoto rats and spontaneously hypertensive rats. Pretreatment with the angiotensin-converting enzyme (ACE) inhibitor captopril markedly enhanced the effect of BK, such that the dose-response curve shifted significantly to the left in all three strains. 3. In a second series of experiments, captopril did not change basal blood pressure, but blocked the pressor response to angiotensin I (AI), but not angiotensin II (AII). 4. The partial agonist Sar1-Ala8-angiotensin II (SAR) increased blood pressure and blocked the pressor response to subsequent AII treatment. 5. After pretreatment with BK (50 micrograms/kg), captopril evoked a decrease in blood pressure, while still blocking the effect of AI. 6. After pretreatment with BK, SAR decreased blood pressure, while still antagonizing the action of AII. 7. These results suggest that ACE plays a role in the inactivation of circulating BK in normotensive and hypertensive rats. Conversely, BK can influence the activity of the renin-angiotensin system, probably by interacting with ACE.

Acetylcholinesterase↗

PubMed1991

Sensitization of baroreceptor reflex by central endothelin in conscious rats.

Effect of centrally administered endothelins (ETs) on cardiovascular regulation was investigated in conscious normotensive rats. ET-1, ET-2, or ET-3 was injected through a cannula into the cisterna magna, and mean arterial pressure (MAP) and heart rate (HR) were measured through a cannula in the femoral artery. Baroreceptor HR reflex was measured by monitoring the changes in HR in response to changes in MAP induced by slow intravenous injection of phenylephrine or nitroprusside. MAP and HR responses were then analyzed in individual animals by sigmoidal curve fitting. Intracisternal (ic) administration of ET-1 did not change resting MAP or HR at doses of 2.5 or 25 pmol/kg. The higher dose of ET-1 induced a significant increase of baroreflex sensitivity without a change of HR range. Sympathetic and vagal components of the baroreflex were examined by testing reflex responses after pretreatment with methylatropine (0.5 mg/kg iv) and atenolol (1.0 mg/kg iv), respectively. An increased baroreflex sensitivity was observed after ET-1 treatment in the atenolol-treated rats but not in the methylatropine-treated rats, suggesting that the peptide selectively affected the vagal component of the reflex. Intravenous 25 pmol/kg ET-1 did not cause an increase in baroreflex sensitivity. Neither ET-2 nor ET-3 (25 pmol/kg ic) induced changes in resting MAP or HR, but both significantly increased baroreflex sensitivity without changes in HR range. Order of potency of the ETs on baroreflex gain was ET-3 greater than or equal to ET-1 greater than ET-2. In conclusion, ETs at doses that do not change resting values for MAP or HR, may induce significant centrally mediated sensitization of the baroreceptor HR reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Role of brain dopamine systems in the development of hypertension in the spontaneously hypertensive rat.

We studied the role of central dopamine in the development of hypertension. Earlier work had shown that depletion of brain dopamine can inhibit the age-related rise in blood pressure in spontaneously hypertensive rats (SHR). In an open-field test, locomotor activity of Wistar-Kyoto controls was inhibited by haloperidol, apomorphine and sulpiride, but these drugs had less effect in SHR. The stimulation-evoked release of [3H]-dopamine from slices of the striatum of SHR was smaller than that from slices of WKY. The inhibition of the stimulation-evoked release of [3H]-dopamine by quinpirole was greater in SHR than in WKY. The results from the lesion experiments and from the behavioural activity studies would suggest an enhanced release of central dopamine in SHR, which might contribute to the development of hypertension in these animals. However, the in vitro release experiments (and subsequent in vivo microdialysis experiments) do not support such an enhanced release but rather showed decreased release of striatal dopamine in SHR.

Animals↗

PubMed1989

Bromocriptine-induced decrease in blood pressure in conscious spontaneously hypertensive rats: evidence for a peripheral site of action.

The aim of the study was to discover whether the dopamine agonist bromocriptine has a central or peripheral site of action on blood pressure. An intraperitoneal injection of bromocriptine (0.5 mg kg-1) induced a long-lasting decrease in blood pressure in conscious spontaneously hypertensive rats (SHR). This effect was blocked by peripheral pretreatment with haloperidol or domperidone, but not by central treatment with haloperidol. A central injection of bromocriptine had only minor effects on blood pressure. These results suggest that primarily peripheral, rather than central, mechanisms are involved in the hypotensive effects of bromocriptine.

Animals↗

PubMed1989

Differential effects of dopaminergic drugs on open-field behavior of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.

Brain catecholamines may play a role in the development of hypertension in the spontaneously hypertensive rat (SHR). To investigate central dopaminergic function in this strain, the effect of various dopaminergic drugs on open-field activity was assessed. In general, basal levels of ambulation were similar in SHRs and their controls, the Wistar-Kyoto rats (WKY). Exploratory rearing activity was increased in SHRs, however. Haloperidol inhibited open-field ambulation in SHRs and WKY, but higher doses were needed in the SHR. Apomorphine inhibited ambulatory activity in WKY but had virtually no effect in SHRs. Amphetamine and the dopamine uptake inhibitor GBR-12909 increased ambulation in SHRs and WKY to a similar extent. Central administration of haloperidol or sulpiride decreased ambulatory activity in WKY, but had no effect in SHRs at the doses used. SCH-23390 decreased ambulation scores both in SHRs and WKY, with the effect being slightly greater in the latter strain. In all cases exploratory rearing was affected as well by the drugs used. The large difference in base-line scores has to be taken into account when interpreting these data, however. Also, for comparison the noradrenergic drugs clonidine and desipramine were tested. Both elicited decreases in activity which were identical in SHRs and WKY. These results show that a number of dopaminergic drugs have differential effects on open-field activity of SHRs as compared to WKY. Ambulatory activity appeared more resistant to inhibition in SHRs than in WKY. The possibility that these results could reflect altered dopaminergic function in SHR involved in the development of hypertension in this strain is discussed.

Amphetamine↗

PubMed1988

Vasopressin and oxytocin gene expression in the supraoptic and paraventricular nucleus of the spontaneously hypertensive rat (SHR) during development of hypertension.

To study the regulation of hypothalamic vasopressin (VP) and oxytocin (OT) gene expression in relation to the development of hypertension, levels of VP mRNA and OT mRNA were determined in spontaneously hypertensive rats (SHR). Differences in VP and OT mRNA content of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of 4- and 10-week-old SHR and Wistar-Kyoto controls (WKY) were quantitated by dot-blot and Northern blot analysis. VP and OT pituitary content and VP plasma levels were measured by radioimmunoassays. VP mRNA levels were approximately 2-fold and 3-fold higher in the SON and PVN of 4-week-old SHR, respectively, as compared to controls. The OT mRNA levels were approximately 35% lower in both nuclei of the SHR. There was no difference in VP and OT pituitary content between 4-week-old SHR and WKY, but VP plasma levels were higher in SHR. In the 10-week-old SHR VP mRNA levels were still approximately 30-40% higher and the OT mRNA levels were approximately 40% lower in both nuclei when compared to age-matched WKY. Pituitary VP and OT contents were respectively 1.5-fold higher and 20% lower in the 10-week-old SHR than in 10-week-old WKY. VP plasma levels were still elevated in the SHR. The data indicate that in the hypothalamo-neurohypophyseal system of the SHR the VP system is in a higher state of activity, while the OT system is lower in activity.

Aging↗

PubMed1988

Open-field behavior of one-clip, two-kidney hypertensive rats: the influence of pre-handling.

The relation between the development of hypertension and changes in behavior was investigated. Hypertension was induced by unilateral application of a 0.20-mm clip around the renal artery. At 4 weeks, but not at 1 week, after the operation an increase in ambulation was found. Blood pressure was significantly increased at 1 (28 mm Hg) and 4 weeks (78 mm Hg) after the operation. In a second experiment, renal hypertensive rats and controls were either regularly handled (i.e., subjected to indirect tail-cuff blood pressure measurements) or left undisturbed. At 4 weeks after clip implantation, only in the nonhandled rats with renal hypertension, an increase in open-field ambulation was found. Blood pressure was markedly increased in both handled and nonhandled renal hypertensive rats.

Animals↗

PubMed1988

Naltrexone and the behavioural action of clonidine in normotensive and spontaneously hypertensive rats.

The present experiments were aimed at the behavioural effects of clonidine and the possible involvement of opiate systems therein. Previous work had shown that opiate antagonists could block the effects of clonidine on blood pressure. In the open-field, clonidine treatment induced a decrease in ambulation and rearing activity. This effect was similar in normotensive Wistar and Wistar-Kyoto rats and in spontaneously hypertensive rats. In neither strain did naltrexone pretreatment influence the behavioural action of clonidine, however. These results do not lend support to the proposed interaction between opiate systems and the central effects of clonidine.

Animals↗

PubMed1988

Open-field behaviour and blood pressure in spontaneously hypertensive rats.

The relation between the development of hypertension and changes in behaviour was investigated. Open-field activity of male and female Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto controls (WKY) was scored at 4, 6 or 10 weeks of age. SHR generally showed higher locomotor activity and exploratory rearing behaviour, but lower grooming activity and defecation. These changes were found for rearing (3-5 fold increase) and grooming scores at all ages, ambulation at 4 weeks and 10 weeks (ambulation-inner) and defecation at 6 and 10 weeks of age. Differences were generally more pronounced in female rats. SHR showed less habituation than WKY. Already at the age of 4 and 6 weeks blood pressure was increased in SHR compared with WKY (approximately 120 mm Hg vs. 100 mm Hg). Between 6 and 10 weeks of age blood pressure increased rapidly in SHR, leading to a marked difference at the latter age (about 40 mm Hg), in both male and female rats. These experiments show that already at a young age, when blood pressure differences with WKY are small, marked behavioural changes are present in SHR. The altered behaviour could play a role in the development of hypertension in SHR.

Animals↗

PubMed1987

Grooming behavior of spontaneously hypertensive rats.

In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar-Kyoto rats (WKY). After i.c.v. injection of 1 microgram ACTH cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the lesser effect of ACTH in SHR was especially prominent for headwashing and anogenital grooming. Moreover, a time course study revealed that the difference between SHR and WKY occurred in the first 6 observation periods of 5 min and thereafter disappeared. The results are discussed in the light of behavioral and central neurochemical differences between SHR and WKY.

Animals↗

PubMed1986

Brain dopamine depletion by lesions in the substantia nigra attenuates the development of hypertension in the spontaneously hypertensive rat.

The involvement of brain dopamine in the development of hypertension in the spontaneously hypertensive rat (SHR) was studied. Intracerebroventricular (i.c.v.) injections of 6-hydroxydopamine (6-OHDA) in young SHR caused depletion of dopamine in frontal cortex and striatum and induced an attenuation of the development of hypertension in SHR. Depletion of noradrenaline and to a lesser extent of serotonin was found as well. The ratio of DOPAC and of HVA to dopamine was increased after 6-OHDA. Pretreatment with the dopamine re-uptake inhibitor GBR-12909 inhibited the effects of 6-OHDA on both blood pressure and brain dopamine content. The effect of 6-OHDA on noradrenaline and serotonin levels were not influenced by pretreatment with GBR-12909. Electrolytic lesions in the substantia nigra delayed the rise in blood pressure in SHR. Lesions in the ventral tegmental area (VTA) were ineffective. After substantia nigra lesions depletion of dopamine was found especially in the nucleus caudatus posterior and the dorsomedial nucleus. After lesions in the VTA substantial dopamine depletion was found in the nucleus accumbens, frontal cortex, lateral septal nucleus and zona incerta. These data suggest that brain dopamine systems play a role in the development of hypertension in SHR and that especially the nigrostriatal system is important in this respect. Moreover, the present results may help to explain the attenuating effect of prehypertensive treatment with 6-OHDA on the development of hypertension.

Animals↗

PubMed1986

Brain noradrenaline and the development of hypertension: the effect of treatment with central 6-hydroxydopamine or DSP-4.

The relative role of brain catecholamines in the development of hypertension in the spontaneously hypertensive rat (SHR) was studied. Treatments consisted in five weeks old SHR of central injections of 6-hydroxydopamine (6-OHDA), 3 X 200 micrograms either intracerebroventricularly (i.c.v.) or intracisternally (i.c.), or of intraperitoneal (i.p.) injections of DSP-4, either once or three times 50 mg/kg. Compared to the pronounced attenuation of the development of hypertension following i.c.v. 6-OHDA treatment, the i.c. 6-OHDA treatment and the multiple DSP-4 treatment were less effective. A single injection of DSP-4 had only minor effects on blood pressure. Heart rate was markedly lower in i.c.v. 6-OHDA treated SHR, but the other treatments induced no effects on this parameter. Noradrenaline depletion was found in various parts of the brain particularly after i.c.v. 6-OHDA or either DSP-4 treatment. Brain dopamine and adrenaline were depleted to a lesser extent. However, the best correlation between blood pressure and brain catecholamine concentration was found for dopamine in the hippocampus and hypothalamus and for adrenaline in the hypothalamus. Noradrenaline levels were also correlated with blood pressure, but to a lesser extent. These results suggest that the depletion of dopamine or adrenaline in the brain may be of more importance in the effects of neurotoxic treatments on the development of hypertension than the effects on brain noradrenaline. Thus, these experiments lend support to the hypothesis that brain noradrenaline systems may not play an important role in the development of hypertension in the SHR.

Animals↗

PubMed1985

Effects of neonatal treatment with monosodium-glutamate in spontaneously hypertensive rats.

Following neonatal treatment with monosodium-glutamate (MSG), blood pressure in adult spontaneously hypertensive rats (SHR) was markedly lower than in control SHR, with only a small decrease in normotensive Wistar-Kyoto controls (WKY). In addition, in MSG-treated SHR an increase in pain-sensitivity was found and both strains showed increased water intake and reduced organ and body weights as compared to vehicle-treated rats.

Animals↗

PubMed1984

Regional brain catecholamine levels and the development of hypertension in the spontaneously hypertensive rat: the effect of 6-hydroxydopamine.

To investigate the role of central catecholaminergic pathways in the development of hypertension in the spontaneously hypertensive rat (SHR) the effects of intracerebroventricular (i.c.v.) injections of 6-hydroxydopamine (6-OHDA) were compared with those of local injections near the main ascending noradrenergic pathways. The parameters studied were systolic blood pressure, heart rate and regional catecholamine concentrations in micropunched brain areas. I.c.v. treatment with 6-OHDA (three 200 micrograms injections) of young SHR attenuated the development of hypertension and caused widespread depletion of noradrenaline and to a lesser extent of dopamine and adrenaline. 6-OHDA-induced lesions of the dorsal and ventral noradrenergic bundles did not affect the rise in blood pressure but induced a depletion of forebrain noradrenaline comparable to that after the i.c.v. treatment. Dopamine and adrenaline levels were, however, not substantially affected. These results suggest that forebrain noradrenergic innervation may not be of major importance for the development of hypertension in the SHR.

Animals↗

PubMedDate not supplied

Role of dopamine in the development of spontaneous hypertension.

To investigate the role of brain catecholamines in the development of spontaneous hypertension, rats were treated with different doses of the neurotoxins 6-hydroxydopamine (6-OHDA) or DSP-4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine hydrochloride). Intracerebroventricular (i.c.v.) 6-OHDA attenuated the development of hypertension in spontaneously hypertensive rats (SHR) and also lowered the systolic blood pressure (BP) in Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Norepinephrine was markedly and dose-dependently depleted in brain areas of all three substrains. Dopamine was affected also, although to a lesser extent. Pretreatment with the norepinephrine-uptake inhibitor desmethylimipramine (DMI) did not influence the effect of 6-OHDA on the development of hypertension in SHR. DMI largely antagonized the 6-OHDA-induced depletion of brain norepinephrine, while dopamine depletion was not affected. Specific depletion of brain norepinephrine by treatment with DSP-4 did not alter the rise in BP in SHR. These results suggest that the effect of 6-OHDA on the development of hypertension in SHR may not be mediated through destruction of brain norepinephrine neurons, but that interruption of brain dopaminergic mechanisms is a possibility in this respect.

Animals↗