In vivo venodilator action of fenoldopam, a dopamine D(1)-receptor agonist.
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.
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Department of Pharmacology, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, V6T 1Z3 B.C., Canada.
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D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018818:Fenoldopam / Q000494:pharmacology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D018491:Dopamine Agonists; D005730:Ganglionic Blockers; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014665:Vasodilator Agents; C009074:N-n-propylnorapomorphine; D008464:Mecamylamine; D018818:Fenoldopam; D001058:Apomorphine