Effect of vasoactive drugs on tumour blood flow as determined by 2H nuclear magnetic resonance spectroscopy.
A selective reduction in tumour blood flow (TBF) could enhance the effects of hyperthermia treatment and of drugs toxic to hypoxic cells. Vasodilator-induced changes in TBF were monitored in transplanted rat fibrosarcomas by non-invasively measuring the uptake of D2O using 2H nuclear magnetic resonance spectroscopy. Hydralazine (1 or 5 mg kg-1) caused a large (45%) reduction in mean arterial blood pressure (MABP) and a 40-60% reduction in TBF. Low-dose hydralazine (0.1 mg kg-1) caused a 20% reduction in MABP but no significant change in TBF. The doses of prazosin (1 mg kg-1) and calcitonin-gene related peptide (CGRP, 1 nmol kg-1) which caused a 20% reduction in MABP led to a 50-60% reduction in TBF. These results demonstrate the advantage of prazosin and CGRP over hydralazine for the reduction of TBF despite a small hypotensive effect. CGRP may be the most suitable of these agents for clinical use because of its short physiological half-life.
Burney
I A
IA
Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London.
Maxwell
R J
RJ
Field
S B
SB
McCoy
C L
CL
Griffiths
J R
JR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001834:Body Water / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D015687:Cell Hypoxia; D003903:Deuterium; D017666:Deuterium Oxide; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000098:blood supply*; D006830:Hydralazine / Q000494:pharmacology*; D006979:Hyperthermia, Induced; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects*; D013997:Time Factors
D006830:Hydralazine; D003903:Deuterium; D017666:Deuterium Oxide; D015740:Calcitonin Gene-Related Peptide; D011224:Prazosin