Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using an in vivo microdialysis method, we found that the extracellular concentrations of dopamine and its main metabolite dihydroxyphenylacetic acid (DOPAC) were lower in the caudate nucleus of 8-week-old spontaneously hypertensive rats (SHR) than in the same area of age-matched normotensive Wistar-Kyoto rats (WKY). No differences in the extracellular concentrations of dopamine and DOPAC were found between renal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats when compared to their respective controls. After subcutaneous administration of the dopamine D2 receptor agonist quinpirole (10, 33 and 100 micrograms/kg), the amount of dopamine and DOPAC in the dialysates was diminished dose dependently. The quinpirole-mediated inhibition of dopamine release was more pronounced in SHR than in WKY, whereas inhibition of the extracellular DOPAC concentration was not different. Compared to WKY, the dose-response curve for the inhibition of dopamine release by quinpirole was shifted to the left in SHR and the maximal inhibition in response to the highest dose was significantly greater. Renal and DOCA-salt hypertensive rats showed no differences in the quinpirole-induced inhibition of the extracellular concentrations of striatal dopamine and DOPAC compared to their controls. The present findings on changes in dopaminergic neurotransmission and D2 autoreceptor-mediated modulation of dopamine release in genetically hypertensive rats but not in rats with experimentally induced hypertension provide further evidence for the hypothesis that alterations in the nigrostriatal dopamine system may be involved in the initiation of the development of spontaneous hypertension.
 ...
PMID:Effect of the dopamine D2 receptor agonist quinpirole on the in vivo release of dopamine in the caudate nucleus of hypertensive rats. 168 54

Using an in vitro superfusion method it was found that nucleus caudatus slices of 8- and 12-week-old spontaneously hypertensive rats (SHR) release significantly less [3H]dopamine and [14C]acetylcholine upon electrical stimulation than do slices of normotensive Wistar-Kyoto rats (WKY) at all frequencies tested. At 4 weeks similar trends were seen, but the difference in [14C]acetylcholine release was not significant. That the difference in release of dopamine was already present prior to the onset of the development of hypertension, i.e. at the age of 4 weeks, indicates that it is probably not a consequence of, but rather associated with the development of hypertension. Addition of the dopamine uptake inhibitor nomifensine to the superfusion medium caused an increase in the net release of [3H]dopamine by inhibiting re-uptake, but did not influence the difference in release between SHR and WKY. The release of labelled dopamine and acetylcholine was inhibited in the presence of the dopamine D2 receptor agonist quinpirole. The concentration-response curve for the inhibition of the release of [3H]dopamine, but not that of [14C]acetylcholine, by quinpirole was shifted to the left and the maximum inhibition was higher for SHR than for WKY. These results suggest that the difference in stimulus-evoked release of labelled dopamine in the nucleus caudatus is not the consequence of changes in the uptake mechanism of dopamine, but is associated with differences between SHR and WKY in dopamine D2 autoreceptor regulation.
 ...
PMID:Electrically stimulated [3H]dopamine and [14C]acetylcholine release from nucleus caudatus slices: differences between spontaneously hypertensive rats and Wistar-Kyoto rats. 213 26

Our previous studies have demonstrated that the specific dopamine D2 receptor agonist, quinpirole (LY171555), has a pressor effect in conscious normotensive rats and that this is accompanied by a centrally mediated increase in sympathetic activity and arginine vasopressin release. This pressor response to quinpirole is blunted in the DOCA/NaCl hypertensive rat. To examine the hypothesis that the responsiveness of the central noradrenergic and serotonergic systems to quinpirole treatment is altered in DOCA/NaCl rats, the norepinephrine (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents of hypothalamic and brainstem areas were measured in 4-week DOCA/NaCl hypertensive and H2O control rats 15 minutes after the intravenous administration of quinpirole (1 mg/kg). The results demonstrate that quinpirole selectively reduced (26%) posterior hypothalamic NE content in control rats, but not in DOCA/NaCl hypertensive rats. The NE content in the spinal cord and 5-HIAA content in the pons were greater in DOCA/NaCl rats than in normotensive controls in both saline and quinpirole treated groups. Our data suggest that the specific D2 agonist may effect its central pressor response by stimulating NE release from posterior hypothalamic area, a "pressor" region of hypothalamus, and that this D2 agonist induced pressor mechanism may be blunted in DOCA/NaCl hypertension.
 ...
PMID:Blunted responsiveness of posterior hypothalamic norepinephrine to quinpirole in DOCA/NaCl hypertensive rats. 244 May 28

Our previous studies have demonstrated: 1) that i.v. quinpirole (LY171555), a selective dopamine D2 receptor agonist, has a dose-dependent pressor effect in conscious rats which is mediated by activation of sympathetic outflow and vasopressinergic activity, and 2) that the activity of central dopaminergic neurons is reduced in deoxycorticosterone acetate (DOCA)/NaCl hypertensive rats. To elucidate the role of central and peripheral dopaminergic systems in the pathogenesis of DOCA/NaCl hypertension, we examined the effects of quinpirole on mean arterial pressure, heart rate, plasma norepinephrine, epinephrine, arginine vasopressin and atrial natriuretic peptide (ANP) in conscious 4-week-old DOCA/NaCl hypertensive and normotensive control rats. Quinpirole (1 mg/kg i.v.) increased mean arterial pressure in both groups, but the pressor response was attenuated in DOCA/NaCl rats. Paradoxically, quinpirole-induced increments in plasma norepinephrine, epinephrine and arginine vasopressin were greater in DOCA/NaCl rats. In addition, quinpirole induced a 2-fold increase in plasma ANP (P less than .01) in both DOCA/NaCl and control rats. Pretreatment with domperidone (2.5 mg/kg i.v.), a peripherally acting dopamine D2 antagonist, enhanced the maximum pressor response to quinpirole in both groups, restored the quinpirole-induced pressor response to control levels in the DOCA/NaCl rats and blocked the stimulatory effect of quinpirole on ANP release in both groups. These data indicate that peripheral dopamine D2 receptors modulate ANP secretion in the rat. The observation that the quinpirole-induced increment in plasma ANP was enhanced in DOCA/NaCl rats supports the hypothesis that the blunted pressor response to quinpirole in this model is related to enhanced ANP release.
 ...
PMID:Blunted pressor responsiveness to quinpirole, a specific dopamine D2 receptor agonist, in conscious deoxycorticosterone acetate/NaCl hypertensive rats is related to atrial natriuretic peptide release. 296 76

Studies were conducted to determine possible development, and underlying mechanisms, of tolerance to the hypotensive effects of ropinirole (4-[2-(dipropylamino)ethyl]-1-3-dihydro-2H-indol-2-one HCl), a selective dopamine receptor agonist, following twice daily oral administration to cynomolgus monkeys and spontaneously hypertensive rats (SHR). Tolerance to the hypotensive effects of the compound developed in both species within one week of repeated dosing. Tolerance which developed in rats was dose-related and could not be attributed to altered plasma/drug concentrations or be overcome by increasing the i.v. challenge dose of ropinirole. Cross-tolerance was shown to the dopamine receptor agonist bromocriptine. Similar hypotensive responses to bethanidine were seen in rats treated with ropinirole or vehicle. Tolerance to hypolocomotor effects of the compound were not apparent in the same time frame. The dopamine D2 receptor antagonist, domperidone, caused hypertension in ropinirole-but not vehicle-treated rats. Results reported in this paper are not consistent with a down-regulation of peripheral dopamine D2-like receptors but suggest a compensatory increase in basal sympathetic tone.
 ...
PMID:Tolerance to peripheral, but not central, effects of ropinirole, a selective dopamine D2-like receptor agonist. 788 25

A series of studies was carried out to characterize the binding properties of dopamine D1 and D2 receptors in membrane homogenates of the caudate nucleus of spontaneously hypertensive rats (SHR). Binding in SHR was studied at the age of 4 weeks when the rats were still in the prehypertensive phase, and at the age of 8 weeks, during the phase in which blood pressure is increasing dramatically; age-matched normotensive Wistar-Kyoto rats (WKY) were used as controls. Binding to dopamine D1 receptors was studied using [3H]SCH 23390. Antagonist binding of dopamine D2 receptors was performed with [3H]spiperone. At both ages no differences were found between SHR and WKY in affinity (Kd) or concentration (Bmax) of dopamine D1 and D2 receptors. Binding to the high affinity state of the dopamine D2 receptor was measured using the agonist [3H]N-n-propylnorapomorphine (NPA). No differences in Bmax or Kd were found between SHR and WKY at both ages studied, indicating that the ratio between dopamine D2 receptors in the high and in the low affinity state is not altered in spontaneous hypertension. Although the results do not reveal differences in affinities or concentrations of dopamine D1 or D2 receptors in the caudate nucleus between SHR and WKY, a role in the development of hypertension for the here described lack of receptor up-regulation in connection with our previous observation of lower release of dopamine in the caudate nucleus of SHR, cannot be excluded.
 ...
PMID:Dopamine D1 and D2 receptors in the caudate nucleus of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. 844 48

The effects of DL-tetrahydropalmatine (THP; a main active substance of the Chinese herb corydalis), haloperidol (a dopamine D2 receptor antagonist), apomorphine and amphetamine on cardiovascular function and striatal dopamine (DA) release were compared in rats under general anesthesia. Intravenous administration of THP (1-10 mg/kg) or haloperidol (0.5-1.25 mg/kg) produced hypotension, bradycardia and increased DA release in the striatum. On the other hand, amphetamine (0.5-1.25 mg/kg) produced hypertension, tachycardia and increased striatal DA release. However, intravenous injection of apomorphine (0.5-1.25 mg/kg) produced hypotension, bradycardia and decreased striatal DA release. In addition, the THP-induced hypotension was attenuated by pretreatment with spinal transection or amphetamine, while the THP-induced bradycardia was attenuated by pretreatment with bilateral vagotomy or amphetamine. Thus, it appears that THP acts through DA D2 receptor antagonism to induce hypotension and bradycardia in rats.
 ...
PMID:DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the inhibition of central nervous dopaminergic mechanisms. 857 17

Neuropeptide Y, a 36-amino-acid peptide, has a wide and specific distribution in the central nervous system. In this study we examined the regulatory mechanisms of neuropeptide Y on dopamine release in the rat central nervous system. The effects of neuropeptide Y on the electrically stimulated [3H]dopamine release were investigated in superfused striatal slices of Sprague-Dawley rats, spontaneously hypertensive rats and Wistar-Kyoto rats. Neuropeptide Y (1 x 10(-8) - 1 x 10(-7) mol/1) reduced the stimulation (1 Hz)-induced [3H]dopamine release by a comparable amount in Sprague-Dawley rats. The blockade of dopamine D2 receptors by the dopamine D2 receptor antagonist, sulpiride, diminished the inhibitory effects of neuropeptide Y on the stimulation-evoked [3H]dopamine release. Pretreatment of slices with pertussis toxin (a potent inhibitor of G1-proteins) attenuated the suppression of the stimulation-evoked [3H]dopamine release by neuropeptide Y. Unlabelled dopamine itself reduced the stimulation-evoked [3H]dopamine release, and the inhibitory effect was also attenuated in the pertussis toxin-pretreated slices. In spontaneously hypertensive rats, the inhibitory effect of neuropeptide Y on the stimulation-evoked [3H]dopamine release was more pronounced than that in Wistar-Kyoto rats. The results of the present study showed that neuropeptide Y inhibited the stimulation-evoked dopamine release partially mediated by dopamine D2 receptors and the pertussis toxin-sensitive G1-proteins in rat striatum. Furthermore, the greater effect of neuropeptide Y on dopamine release in spontaneously hypertensive rats suggests a possible involvement of the peptide in regulating the central dopaminergic nerve activity in hypertension.
 ...
PMID:Modulation of [3H]dopamine release by neuropeptide Y in rat striatal slices. 908 79

1. Systemic administration of a dopamine D2 receptor agonist, such as quinpirole, causes a centrally mediated rise in blood pressure (BP) with a maximum at 1-2 min after injection. At 30 min after injection, when BP has returned to baseline, further treatment with these drugs has little effect on BP. Moreover, the antihypertensive effects of sympathoinhibitory drugs, such as clonidine and rilmenidine, is markedly inhibited. Increased circulating levels of vasopressin contribute to the initial rise in BP, but return to baseline thereafter. Differential changes in sympathetic vasomotor tone may be involved in the apparent desensitization induced by quinpirole. 2. Stimulation of the region of origin of the mesolimbic dopamine (DA) system in the brain, the ventral tegmental area, causes a long-lasting increase in BP. In this model, circulating levels of vasopressin are moderately increased through a non-dopaminergic mechanism. Dopaminergic stimulation causes a functional potentiation of the effect of vasopressin, resulting in an increase in BP. 3. Spontaneously hypertensive rats (SHR) display several changes in central dopaminergic responses. Dopamine levels in the brain are normal, while resting DA activity appears reduced. Partial depletion of forebrain DA levels, particularly in the nigrostriatal system, causes an inhibition of the development of hypertension and normalizes deficient functional responses to dopaminergic drugs in the SHR. 4. These results show that brain DA is involved in several aspects of cardiovascular regulation and may be involved in the development of hypertension. The widespread involvement of brain DA systems in behavioural, hormonal and cardiovascular mechanisms suggests that these systems play an important role in the integration of stress and environmental stimuli with homeostatic mechanisms in the body.
 ...
PMID:Pressor responses to brain dopaminergic stimulation. 931 86

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.
 ...
PMID:Brain dopamine D2 receptor mRNA levels are elevated in young spontaneously hypertensive rats. 1057 42


1 2 Next >>