The modification of blood flow in tumours and their supplying arteries by nicotinamide.
We have studied the ability of the radiosensitizer nicotinamide (NA) to alter the contractility of normal and tumour blood vessels using an ex vivo isolated artery perfusion system. NA at a concentration of 8.2 mM reduced the constrictions produced by phenylephrine (PE) by 2-fold in both normal epigastric arteries and those that had been supplying p22 tumours in BD9 rats. At that same concentration NA also attenuated the spontaneous, rhythmic contractions that were seen in many tumour arteries. When the tumour arteries were perfused together with the tumour they supplied NA had little effect on the flow resistance of the tumour vascular network but reduced the resistance by up to 30% when the arteries were preconstricted with phenylephrine. These direct effects on vascular resistance together with the reduction of interstitial fluid pressure could combined to improve the homogeneity of tumour perfusion.
Hirst
D G
DG
Department of Biomedical Sciences, University of Ulster, Newtownabbey, Co. Antrim, Northern Ireland.
Kennovin
G D
GD
Tozer
G M
GM
Prise
V E
VE
Flitney
E W
EW
D000230:Adenocarcinoma / Q000098:blood supply*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009536:Niacinamide / Q000494:pharmacology*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D010656:Phenylephrine; D009536:Niacinamide