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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 314 (1980), S. 177-182 
    ISSN: 1432-1912
    Keywords: Dopamine ; Renal vasodilation ; Metoclopramide ; Competitive antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The interaction of metoclopramide with renal dopamine receptors has been characterized in anesthetized dogs surgically prepared with arterial blood pressure catheters and renal artery blood flowprobes. In normal dogs, i. v. dopamine (3 μg/kg) produced consistent and selective decrements in renal vascular resistance (RVR) and increments in renal blood flow over a 220 min test period; mean arterial blood pressure and cardiac rate were minimally affected. Pretreatment with metoclopramide, 1 and 10 mg/kg i. v., resulted in dose-related inhibition (maximum inhibition 44% and 94%, respectively) of the renal vasodilator activity of dopamine without altering baseline parameters. The duration of antagonism produced by 1 mg/kg of metoclopramide was approximately 30 min, while 10 mg/kg resulted in significant attenuation for the entire test period. Decreases in RVR produced by prostaglandin A1 (0.03 and 0.3 μg/kg, i. v.) and bradykinin (3 and 15 μg/kg, i. v.) that were comparable to those of dopamine were unaltered by metoclopramide. Furthermore, metoclopramide did not affect the diastolic blood pressure responses to noradrenaline (0.1–3 μg/kg, i. v.) or isoproterenol (0.03–0.3 μg/kg, i. v.), nor did it alter dopamine-induced vasoconstriction of the iliac vasculature. In phenoxybenzamine (3 mg/kg, i. v.) treated dogs, dopamine (0.3–30 μg/kg, i. v.) produced dose-related reductions in RVR. Administration of metoclopramide (10 mg/kg, i. v.) resulted in a 10-fold parallel displacement, to the right, of the RVR dose-response curve to dopamine. These findings demonstrate that metoclopramide is an effective antagonist of renal dopamine receptors following systemic administration in the dog. The results are not consistent with the classification of metoclopramide as a selective antagonist of D-2 receptors.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 321 (1982), S. 63-69 
    ISSN: 1432-1912
    Keywords: N,N-di-n-propyldopamine ; Dopamine receptors ; Hypotension ; Bradycardia ; Propranolol ; Nitroglycerin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intravenous infusion of N,N-di-n-propyldopamine (DPDA) (100–900 μg/kg) produced dose-related arterial hypotension which was accompanied by bradycardia at higher doses. Increments in arterial blood pressure induced by carotid artery occlusion were attenuated during administration of DPDA (600 μg/kg, i.v.), whereas cardiovascular compensation to postural change remained unaltered. DPDA-induced hypotension and its attenuation of carotid occlusion responses were prevented by pretreatment with sulpiride (0.5 mg/kg, i.v.), indicating involvement of dopamine receptors in these activities. Hemodynamic studies demonstrated that DPDA (600 μg/kg, i.v.) lowered mean arterial blood pressure by dilating the systemic vasculature; mean aortic blood flow increased in the presence of bradycardia due to an increment in stroke volume. Left ventricular minute work, stroke work and myocardial oxygen consumption were decreased as a consequence of the hypotension and bradycardia produced by DPDA. The results of other experiments illustrated that propranolol (0.5 mg/kg, i.v.) and nitroglycerin (40 μg/kg, i.v.) administered in combination, but not individually, resulted in hemodynamic alterations similar to those of DPDA (600 μg/kg, i.v.). However, at equivalent reductions in mean arterial blood pressure, cardiac rate and myocardial oxygen consumption only DPDA increased mean aortic blood flow and lowered left ventricular end-diastolic pressure. The hemodynamic effects produced by DPDA are interpreted to be a reflection of its known ability to inhibit neurogenic release of noradrenaline by stimulation of neuronal dopamine receptors. The composite data suggest that orally effective dopamine receptor agonists may have clinical utility as antihypertensive agents with minimal liability for producing orthostasis. Furthermore, a potential use in ischemic heart disease is suggested by data indicating that DPDA maintained systemic perfusion at reduced levels of myocardial work and oxygen consumption.
    Type of Medium: Electronic Resource
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