Antagonism of the renal vasodilator activity of dopamine by metoclopramide

Hahn, R; Wardell, Joe R.

doi:10.1007/bf00504535

Cited by 20 publications

(7 citation statements)

References 17 publications

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“…The lack of antagonism of DA, receptors by doses of metoclopramide up to 145 /ug/kg in the present study is not inconsistent with reports that metoclopramide does antagonize DA, receptors when given in comparable doses directly into the renal artery 7 or when given intravenously, but in much higher doses (1000-10,000 /ng/kg). 26 The finding of a dosedependent antagonism of DA 2 versus DA, receptors by metoclopramide suggests that the affinity of this dopamine antagonist for the DA 2 receptor is greater than that for the DA, receptor. The results of the present study differ somewhat from those reported by Hamed et al 12 for PBDA.…”

Section: Emetic Potency Of N-alkyl Substituted Dopamine Analogs In Comentioning

confidence: 99%

Activation of peripheral dopamine presynaptic receptors lowers blood pressure and heart rate in dogs.

Taylor¹,

Fennell²,

Feldman³

et al. 1983

Hypertension

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SUMMARY Previous studies have identified several N,N-dialkyl substituted analogs of dopamine that lower blood pressure and cause renal and femoral vasodilation by activation of noradrenergic neuronal dopaminergic receptors that inhibit further release of norepinephrine (presynaptic DA 2 ) or of vasodilatory dopaminergic receptors located in vascular beds (postsynaptic DA|). Unlike dopamine itself, these analogs demonstrate minimal /3,-adrenergic receptor activation and a!-vasoconstrictor effect. In the present study, we have compared the relative hemodynamic, renal and emetic properties of four of these dopamine analogs in anesthetized and/or conscious dogs. The purposes of the studies were: 1) determination of the relative contribution of central versus peripheral nervous system sites of action of these analogs to their effects on cardiovascular function; 2) assessment of the relative importance of activation of DA, versus DA 2 receptors for the observed hemodynamic effects; and 3) investigation of the relative efficacy of dopamine antagonists for DA 2 versus DA, receptors. The reduction in blood pressure, increase in renal blood flow, and decrease in renal vascular resistance produced by propylbutyl -(PBDA), ethylbutyl-(EBDA), or propylpentyl-(PPDA) dopamine was similar to that reported previously for dipropyldopamine (DPDA). All analogs except PPDA also lowered heart rate. Doses of either the peripheral dopamine receptor antagonist, domperidone, or the peripheral and central dopamine receptor antagonist, metoclopramide, which attenuated PBDA-induced reductions in mean arterial pressure and heart rate did not antagonize the increase in renal blood flow produced by this analog. Following electrical stimulation of the cardioaccelerator nerve, all four dopamine analogs reduced the heart rate of spinally transected, vagotomized, anesthetized dogs. In addition, ( -)-sulpiride but not phentolamine antagonized the reduction in both heart rate and coronary sinus norepinephrine secretion produced by PBDA during cardioaccelerator nerve stimulation. In conscious dogs, the emetic potency was: DPDA > PPDA = PBDA > EBDA. The dopamine receptor antagonist, (-)-sulpiride, completely abolished the emesis induced by PBDA administration. These results indicate that PBDA and other N,N-dialkyl substituted dopamine derivatives can alter cardiovascular hemodynamics primarily by agonism of peripheral dopamine receptors. Furthermore, PBDA appears to lower blood pressure primarily through agonism of presynaptic DA 2 receptors rather than postsynaptic DA, vascular receptors. (Hypertension 5: 226-234, 1983) KEY WORDS • propylbutyldopamine * dopamine analogs • sulpiride • domperidone dopamine antagonists • postsynaptic dopamine receptors • renal blood flow D pPAMINERGIC agonists that decrease sympathetic neuronal release of norepinephrine by activation of specific inhibitory receptors

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Section: Emetic Potency Of N-alkyl Substituted Dopamine Analogs In Comentioning

confidence: 99%

Activation of peripheral dopamine presynaptic receptors lowers blood pressure and heart rate in dogs.

Taylor¹,

Fennell²,

Feldman³

et al. 1983

Hypertension

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“…Metoclopramide is a drug which mainly blocks the DA2 receptors [10] although at the dose employed in our study it can also block DAi receptors [22], During placebo administration, metoclopramide did not influence blood pressure and heart rate, slightly but not significantly decreased glomerular filtration rate, while renal plasma flow reduction was statistically signif icant; plasma noradrenaline and plasma renin activity were slightly but not significantly increased and plasma aldosterone significantly augmented. Some of these ef fects can be attributed to the blockade of DA2 receptors, as it is known that the activation of these receptors increases glomerular filtration rate [23] and inhibits aldosterone secretion [8,[24][25][26][27]; the significant decrease in renal plasma flow might be due either to activation of renal nerves (as DA2 receptor-mediated sympathetic in hibition [6,9,28]) or more probably to the blockade of renal DA!…”

Section: Discussionmentioning

confidence: 90%

Antihypertensive and Renal Effects of Tertatolol, a New Beta-Blocking Agent, in Hypertensive Patients

et al. 1986

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Tertatolol, a new nonselective β-adrenoceptor blocker, was administered to 11 hypertensive patients in a short-term study. Systolic and diastolic blood pressure and heart rate were significantly decreased when compared to the placebo period: in spite of that glomerular filtration rate and renal plasma flow were unchanged. The administration of metoclopramide (a dopaminergic receptor antagonist) caused a significant reduction of renal plasma flow and a significant rise of renal vascular resistances during placebo, but no change during tertatolol therapy. A possible interference of tertatolol on dopaminergic receptors is discussed as the mechanism reponsible for the unmodified renal plasma flow despite the significant blood pressure lowering with tertatolol.

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“…In the present study we therefore reinvesti gated the effects of the predominant DA-2 receptor blocker MCP [40] in conscious rats. MCP had no effect on plasma ANP concen tration, urine flow or sodium excretion under control conditions, during gradual ECFV ex pansion or during stable ECFV expansion equal to a 10% increase in body weight.…”

Section: Discussionmentioning

confidence: 99%

Metoclopramide Does Not Affect Renal Function and Atrial Natriuretic Peptide Release in Response to Acute Saline Loading in Conscious Rats

Nati¹,

Campean²,

Kramer³

1994

Pharmacology

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It was previously shown in man that metoclopramide (MCP), a dopamine (DA)-2 receptor blocker, attenuates the natriuresis of water immersion. In the present study, we therefore investigated the effects of MCP on renal function and atrial natriuretic peptide (ANP) release in conscious rats. Under basal conditions MCP did not affect glomerular filtration rate (GFR)(7.4 ± 1.7 ml/min/kg without and 7.8 ± 0.6 ml/min/kg with MCP), urinary fractional excretion of Na (FE_Na) (0.3 ± 0.1% without and 0.3 ± 0.1% with MCP) and K (FE_K) (20.6 ± 1.4% without and 28.0 ± 6.2% with MCP) or plasma ANP (37 ± 5 pmol/l without and 31 ± 6 pmol/l with MCP). During acute saline loading equal to a 10% rise in body weight, which significantly (p < 0.05) increased GFR, MCP again had no effects on GFR (8.8 ± 1.8 ml/min/kg with vs. 9.7 ± 2.5 ml/ min/kg without MCP), FE_Na (24.5 ± 6.9% with vs. 20.4 ± 5.1% without MCP), FE_K (52.5 ± 6.9% with vs. 52.5 ± 9.5% without MCP) and plasma ANP (89 ± 8 pmol/l with vs. 91 ± 9 pmol/l without MCP). These results indicate that DA does not modulate renal function or ANP release via DA-2 receptors under basal conditions nor in response to acute saline loading in conscious rats.

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Antagonism of the renal vasodilator activity of dopamine by metoclopramide

Cited by 20 publications

References 17 publications

Activation of peripheral dopamine presynaptic receptors lowers blood pressure and heart rate in dogs.

Activation of peripheral dopamine presynaptic receptors lowers blood pressure and heart rate in dogs.

Antihypertensive and Renal Effects of Tertatolol, a New Beta-Blocking Agent, in Hypertensive Patients

Metoclopramide Does Not Affect Renal Function and Atrial Natriuretic Peptide Release in Response to Acute Saline Loading in Conscious Rats

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