Contractile properties of human renal cell carcinoma recruited arteries and their response to nicotinamide

Background and purpose: The manipulation of tumour blood supply and thus ox ygenation is a potentially important strategy for improving the treatment o f solid tumours by radiation. Increased knowledge about the characteristics that distinguish the tumour vasculature from its normal counterparts may e nable tumour blood flow to be more selectively modified, Nicotinamide (NA) causes relaxation of preconstricted normal and tumour-supply arteries in ra ts. It has also been shown to affect microregional blood flow in human tumo urs. Direct effects of NA on human tumour supply arteries have not previous ly been reported. This paper describes our evaluation of the effects of NA on two parameters: 'spontaneous', oscillatory contractile activity and agon ist (phenylephrine)-induced constriction in the arteries supplying human re nal cell carcinomas. Materials and methods: Isolated renal cell carcinoma feeder vessels were pe rfused in an organ bath with the alpha(1)-adrenoceptor agonist phenylephrin e (PE). When the arteries had reached a plateau of constriction, nicotinami de (8.2 mM) was added to the perfusate and changes in perfusion pressure we re measured. Results: PE (10 mu M) induced a sustained constriction in the majority of t he renal cell carcinoma feeder vessels examined, demonstrating that they re tain contractile characteristics, at least in response to this alpha(1)-adr enoceptor agonist. In combination with NA (8.2 mM) the constriction was sig nificantly attenuated in half of the preparations. In addition, seven arter ies exhibited spontaneous contractile activity which was significantly atte nuated by NA in six of them. Conclusions: NA can significantly attenuate both 'spontaneous' and agonist- induced constrictions in tumour-recruited human arteries, though not all ar teries are sensitive. Published by Elsevier Science Ireland Ltd.