Peripheral dopamine receptors, potential targets for a new class of antihypertensive agents

Cavero, Icilio; Massingham, R.; Lefèvre-Borg, F

doi:10.1016/0024-3205(82)90078-9

Cited by 73 publications

(25 citation statements)

References 27 publications

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“…Thus, the finding that bromocriptine-induced hypotension could be attenuated by pretreatment with iv domperidone suggests that this effect is mediated, at least in part, through a peripheral D2 dopaminergic mechanism, resulting in a decrease in sympathetic noradrenergic neurotransmission. This sympathoinhibitory action may result from activation of peripheral dopamine Dz receptors located either at sympathetic ganglia and/or presynaptic sites [43][44][45]. The present investigation did not attempt to determine whether the peripheral receptors are located in sympathetic ganglia or on the postsympathetic nerve endings.…”

Section: Discussionmentioning

confidence: 99%

Hypotensive action of bromocriptine in the DOCA‐salt hypertensive rat: Contribution of spinal dopamine receptors

Lahlou

Duarte

1998

Fundamemntal Clinical Pharma

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To assess the role of spinal dopamine receptors in mediation of hypotension induced by systemic administration of the dopamine D2 receptor agonist, bromocriptine, conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rats were pretreated with either intravenous (i.v.; 500 micrograms/kg) or intrathecal (i.t.; 40 micrograms/rat at T9-T10) domperidone, a selective dopamine D2 receptor antagonist that does not cross the blood-brain barrier. In DOCA-salt hypertensive rats, i.v. administration of a sub-maximal dose of bromocriptine (150 micrograms/kg) induced a significant decrease in mean aortic pressure (MAP) which was greater and longer lasting than that in uninephrectomized control rats. Intravenous or i.t. pretreatment with domperidone reduced partially, but significantly, the hypotensive effect of bromocriptine (reduction of about 57% and 45% of the maximal effect, respectively). The remaining responses observed during the 60 min postinjection period were still statistically significant as compared with vehicle injection. In contrast, the bromocriptine-induced hypotension was fully abolished by i.v. pretreatment with metoclopramide (300 micrograms/kg), a dopamine D2 receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with i.v. and i.t. domperidone. These results suggest that, in DOCA-salt hypertensive rats, the hypotension induced by i.v. bromocriptine is mediated partly through a peripheral D2 dopaminergic mechanism and partly through stimulation of spinal dopamine D2 receptors, has been demonstrated in conscious normotensive rats.

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Section: Discussionmentioning

confidence: 99%

Hypotensive action of bromocriptine in the DOCA‐salt hypertensive rat: Contribution of spinal dopamine receptors

Lahlou

Duarte

1998

Fundamemntal Clinical Pharma

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“…Quinpirole injected i.v. into anaesthetized rats also caused a depressor response (Sengupta & Lokhandwala, 1985;Nagahama et al, 1986b;Cavero et al, 1987). It has also been shown by Damase-Michel et al (1990) that i.v.…”

Section: Discussionmentioning

confidence: 89%

“…Since the rats were ganglion-blocked with mecamylamine, the tachycardic response elicited by the highest dose of either fenoldopam or R(7)-propylnorapomorphine was likely due to a direct positive chronotropic action. In this respect, a direct positive chronotropic action of quinpirole (Damase-Michel et al, 1990) and fenoldopam (Cavero et al, 1987) has been reported.…”

Section: Discussionmentioning

confidence: 97%

In vivo venodilator action of fenoldopam, a dopamine D₁‐receptor agonist

Pang

2000

British J Pharmacology

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1 The e ects of the dopamine D 1 -receptor agonist fenoldopam were compared with those of the D 2 -receptor agonist R(7)-propylnorapomorphine and vehicle on mean arterial pressure (MAP), mean circulatory ®lling pressure (MCFP, the driving force of venous return), arterial resistance (R a ), venous resistance (R v ), heart rate (HR) and cardiac output (CO) in groups of thiobutabarbitoneanaesthetized rats pre-treated with i.v. injection of mecamylamine (3.7 mmol kg 71 ) and continuously infused with noradrenaline (6.8 nmol kg 71 min 71 ). 2 The vehicle did not alter any haemodynamic variables. All doses of fenoldopam (0.5, 2 and 16 mg kg 71 min 71 ) reduced MAP, R a and R v , and increased CO. At the highest dose, fenoldopam also increased HR and reduced MCFP. 3 All doses of R(7)-propylnorapomorphine (0.5, 2 and 16 mg kg 71 min 71 ) increased MAP but did not signi®cantly alter CO, R v and MCFP. Both R a and HR were increased by the highest dose of R (7)-propylnorapomorphine. 4 Our results indicate that fenoldopam reduces MAP and MCFP, and markedly increases CO through reductions of arterial and venous resistances. The e ects of fenoldopam in dilating arterial resistance and capacitance vessels were similar. In contrast, R(7)-propylnorapomorphine elevates MAP through an increase in arterial resistance but has minimal e ects on CO, MCFP and venous resistance. Both drugs have a small direct, positive chronotropic action at the highest dose.

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“…This compound was recently shown to be a potent agonist at prejunctional dopamine receptors in the central and peripheral nervous systems (Anden et al, 1982;Willfert et al, 1984). Numerous studies have shown that certain dopamine receptor agonists such as lergotrile, N, N-di-n-propyldopamine (DPDA) and pergolide reduce blood pressure in conscious spontaneously hypertensive rats and a number of anaesthetized animal preparations (for review see Cavero et al, 1982b). These cardiovascular effects are thought to be due to stimulation of DA2-dopamine receptors at prejunctional sites on axonal varicosities of postganglionic sympathetic nerves (Cavero et al, 1982a), as they can be antagonized by drugs which preferentially block the DA2-dopamine receptor, such as S-sulpiride RS-sulpiride and haloperidol (Barrett & Lockhandwala, 1981;Cavero et al, 1982b).…”

Section: Discussionmentioning

confidence: 99%

“…doses of idazoxan used have been shown in previous experiments to be selective for M2-adrenoceptors, and also to inhibit effectively the cardiovascular effects of clonidine in anaesthetized rats (Berridge et al, 1982;Doxey et al, 1983;Brown & Harland, 1984). Sulpiride was given at doses that antagonize both the cardiovascular actions of, and behavioural responses to DA2-dopamine receptor agonists (Sved & Fernstrom, 1980;Barrett & Lockhandwala, 1981;Cavero, 1981;Cavero et al, 1981aCavero et al, , 1982aCavero et al, ,b, 1984Nishibe et al, 1982).…”

Section: Administration Of Drugsmentioning

confidence: 99%

B‐HT 958 lowers blood pressure and heart rate in the rat through stimulation of dopamine receptors

Harland

1986

British J Pharmacology

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ITo investigate whether the hypotensive and bradycardiac effects of B-HT 958 (2-amino-6-(pchlorobenzyl)- 4H-5,6,7,8-tetrahydrothiazolo-(5,4-d) A combination of idazoxan 1000 pLg kg-' i.v. and sulpiride 300 Lg kg-' i.v. did not cause further significant inhibition of B-HT 958 hypotension and bradycardia compared with sulpiride 300 pg kg-' i.v. alone. This combination however had a significantly greater effect in inhibiting B-HT 958 hypotension than had idazoxan 1OOOpg kg-' alone, and almost completely blocked the B-HT 958-induced fall in plasma noradrenaline concentration. 6 These results suggest that in the anaesthetized rat the cardiovascular effects of B-HT 958 are due to stimulation of dopamine receptors, probably located within the central nervous system, and not to stimulation of peripheral prejunctional 2-adrenoceptors.

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Peripheral dopamine receptors, potential targets for a new class of antihypertensive agents

Cited by 73 publications

References 27 publications

Hypotensive action of bromocriptine in the DOCA‐salt hypertensive rat: Contribution of spinal dopamine receptors

Hypotensive action of bromocriptine in the DOCA‐salt hypertensive rat: Contribution of spinal dopamine receptors

In vivo venodilator action of fenoldopam, a dopamine D₁‐receptor agonist

B‐HT 958 lowers blood pressure and heart rate in the rat through stimulation of dopamine receptors

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Peripheral dopamine receptors, potential targets for a new class of antihypertensive agents

Cited by 73 publications

References 27 publications

Hypotensive action of bromocriptine in the DOCA‐salt hypertensive rat: Contribution of spinal dopamine receptors

Hypotensive action of bromocriptine in the DOCA‐salt hypertensive rat: Contribution of spinal dopamine receptors

In vivo venodilator action of fenoldopam, a dopamine D1‐receptor agonist

B‐HT 958 lowers blood pressure and heart rate in the rat through stimulation of dopamine receptors

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In vivo venodilator action of fenoldopam, a dopamine D₁‐receptor agonist