Effects of intravenous infusion of dopamine on tumor blood flow in rat subcutis.
To determine the effects of intravenous administration of dopamine hydrochloride (DA) on tumor blood flow (TBF), we measured the blood flow of normal subcutaneous tissue and subcutaneous tumor (LY-80, a variant of Yoshida sarcoma) in enflurane-anesthetized male Donryu rats using a hydrogen clearance method. Measurements were made before and during intravenous infusion of DA at a rate of 5 micrograms/kg/min, while recording the mean arterial blood pressure of the rats. Under mild hypertension induced by DA, the blood flow of normal subcutis decreased and TBF increased significantly. SCH-23390, an antagonist of the DA1 receptor, inhibited the enhancement of TBF by DA; while domperidone, an antagonist of the DA2 receptor, did not modify the effects of DA. In experimental chemotherapy against the tumor using adriamycin (ADM) 5 mg/kg i.v., only the combination of DA and ADM significantly inhibited the tumor growth. Moreover, DA reduced the weight loss caused by ADM. These results indicate that DA could have a role in increasing TBF and possibly enhance drug delivery to tumors. Moreover, it appears that the DA1 receptor contributes, at least in part, to the enhanced blood flow in rat subcutaneous tumor following DA administration.
Tanda
S
S
Department of Tumor Microcirculation, Tohoku University, Sendai.
Hori
K
K
Saito
S
S
Zhang
Q H
QH
Li
H C
HC
Suzuki
M
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012517:Sarcoma, Yoshida / Q000098:blood supply*; D012867:Skin / Q000098:blood supply
D001552:Benzazepines; D004294:Domperidone; D004317:Doxorubicin; D004298:Dopamine