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

MW Ruddock, DM Burns, Caroline McKeown, L Murphy, IK WAlsh, PF Keane, DG Hirst*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Background and purpose: The manipulation of tumour blood supply and thus oxygenation is a potentially important strategy for improving the treatment of solid tumours by radiation. Increased knowledge about the characteristics that distinguish the tumour vasculature from its normal counterparts may enable tumour blood flow to be more selectively modified, Nicotinamide (NA) causes relaxation of preconstricted normal and tumour-supply arteries in rats. It has also been shown to affect microregional blood flow in human tumours. Direct effects of NA on human tumour supply arteries have not previously been reported. This paper describes our evaluation of the effects of NA on two parameters: 'spontaneous', oscillatory contractile activity and agonist (phenylephrine)-induced constriction in the arteries supplying human renal cell carcinomas.

Materials and methods: Isolated renal cell carcinoma feeder vessels were perfused in an organ bath with the alpha(1)-adrenoceptor agonist phenylephrine (PE). When the arteries had reached a plateau of constriction, nicotinamide (8.2 mM) was added to the perfusate and changes in perfusion pressure were measured.

Results: PE (10 mu M) induced a sustained constriction in the majority of the renal cell carcinoma feeder vessels examined, demonstrating that they retain contractile characteristics, at least in response to this alpha(1)-adrenoceptor agonist. In combination with NA (8.2 mM) the constriction was significantly attenuated in half of the preparations. In addition, seven arteries exhibited spontaneous contractile activity which was significantly attenuated 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 arteries are sensitive. Published by Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)179-184
Number of pages6
JournalRadiotherapy and Oncology
Volume54
Issue number2
Publication statusPublished - Feb 2000

Keywords

  • nicotinamide
  • human tumours
  • radiosensitizer
  • blood flow
  • TUMOR BLOOD-FLOW
  • INTERSTITIAL FLUID PRESSURE
  • OXIDE SYNTHASE ACTIVITY
  • NITRIC-OXIDE
  • SOLID TUMORS
  • ACCELERATED RADIOTHERAPY
  • CANCER
  • OXYGEN
  • RADIOSENSITIZATION
  • ANGIOGENESIS

Cite this