The effect of docarpamine, a dopamine pro-drug, on blood pressure and catecholamine levels in spontaneously hypertensive rats.
We studied the effects of bolus intravenous injection of the dopamine prodrug, docarpamine (200 microg/kg), on mean arterial pressure (MAP) and heart rate (HR) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). In WKY rats (n=18), MAP and HR increased 5 min after docarpamine and then returned to baseline levels within 15 min. In contrast, in SHRs (n=15), MAP and HR gradually decreased, reaching a nadir 20 min after injection. Five min after docarpamine, plasma dopamine and 3,4-dihydroxy phenyl acetic (DOPAC) levels increased in both WKY rats (n=5) and SHRs (n=5). The docarpamine-induced changes in MAP and HR in both rat strains (n=5/strain) were blocked by the D1-like antagonist, SCH23390. alpha-Adrenergic (n=4) and vasopressin V1 (n=3) receptor blockade also abrogated the effects of docarpamine in WKY rats. We conclude that docarpamine differentially affects MAP and HR in WKY and SHRs. In SHRs, the depressor and bradycardiac effects of docarpamine are mediated by D1-like receptors. In WKY rats, the pressor and tachycardiac responses are caused by an interaction among D1-like, alpha-adrenergic, and V1 receptors.
Sanada
H
H
Department of Pathology, The University of Virginia Health Sciences Center, Charlottesville, USA.
Asico
L D
LD
Shigetomi
S
S
Tanaka
K
K
Niimura
S
S
Watanabe
H
H
Goldstein
D S
DS
Felder
R A
RA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood*; D002396:Catechols / Q000097:blood; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors
D000317:Adrenergic alpha-Antagonists; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D002395:Catecholamines; D002396:Catechols; D018492:Dopamine Antagonists; D006727:Hormone Antagonists; D011355:Prodrugs; D017447:Receptors, Dopamine D1; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; C052143:docarpamine; D004298:Dopamine; D010646:Phentolamine