In vivo venodilator action of fenoldopam, a dopamine D(1)-receptor agonist. 2000

S S Ng, and C C Pang
Department of Pharmacology, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, V6T 1Z3 B.C., Canada.

The effects of the dopamine D(1)-receptor agonist fenoldopam were compared with those of the D(2)-receptor agonist R(-)-propylnorapomorphine and vehicle on mean arterial pressure (MAP), mean circulatory filling 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 thiobutabarbitone-anaesthetized rats pre-treated with i.v. injection of mecamylamine (3.7 micromol kg(-1)) and continuously infused with noradrenaline (6.8 nmol kg(-1) min(-1)). The vehicle did not alter any haemodynamic variables. All doses of fenoldopam (0.5, 2 and 16 microgram kg(-1) min(-1)) reduced MAP, R(a) and R(v), and increased CO. At the highest dose, fenoldopam also increased HR and reduced MCFP. All doses of R(-)-propylnorapomorphine (0.5, 2 and 16 microgram kg(-1) min(-1)) increased MAP but did not significantly alter CO, R(v) and MCFP. Both R(a) and HR were increased by the highest dose of R(-)-propylnorapomorphine. Our results indicate that fenoldopam reduces MAP and MCFP, and markedly increases CO through reductions of arterial and venous resistances. The effects of fenoldopam in dilating arterial resistance and capacitance vessels were similar. In contrast, R(-)-propylnorapomorphine elevates MAP through an increase in arterial resistance but has minimal effects on CO, MCFP and venous resistance. Both drugs have a small direct, positive chronotropic action at the highest dose.

UI MeSH Term Description Entries
D008297 Male Males
D008464 Mecamylamine A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.
D011311 Pressoreceptors Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. Baroreceptors,Receptors, Stretch, Arterial,Receptors, Stretch, Vascular,Stretch Receptors, Arterial,Stretch Receptors, Vascular,Arterial Stretch Receptor,Arterial Stretch Receptors,Baroreceptor,Pressoreceptor,Receptor, Arterial Stretch,Receptor, Vascular Stretch,Receptors, Arterial Stretch,Receptors, Vascular Stretch,Stretch Receptor, Arterial,Stretch Receptor, Vascular,Vascular Stretch Receptor,Vascular Stretch Receptors
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002302 Cardiac Output The volume of BLOOD passing through the HEART per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with STROKE VOLUME (volume per beat). Cardiac Outputs,Output, Cardiac,Outputs, Cardiac
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005730 Ganglionic Blockers Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. Ganglionic Blocking Agents,Ganglioplegic Agents,Blocking Agents, Ganglionic,Ganglionic Blockaders,Agents, Ganglionic Blocking,Agents, Ganglioplegic,Blockaders, Ganglionic,Blockers, Ganglionic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001058 Apomorphine A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. Apokinon,Apomorphin-Teclapharm,Apomorphine Chloride,Apomorphine Hydrochloride,Apomorphine Hydrochloride Anhydrous,Apomorphine Hydrochloride, Anhydrous,Apomorphine Hydrochloride, Hemihydrate,Britaject,Apomorphin Teclapharm
D014655 Vascular Resistance The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT. Peripheral Resistance,Total Peripheral Resistance,Pulmonary Vascular Resistance,Systemic Vascular Resistance,Peripheral Resistance, Total,Resistance, Peripheral,Resistance, Pulmonary Vascular,Resistance, Systemic Vascular,Resistance, Total Peripheral,Resistance, Vascular,Vascular Resistance, Pulmonary,Vascular Resistance, Systemic

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