title: Nitric oxide inhibition sustains vasopressin-induced vasoconstriction.
abstract: Hepatic parenchymal vasoconstriction increases cytotoxic drug uptake into hepatic metastases by increasing the tumour to liver blood flow ratio. Prolonged infusion of the vasoconstrictor vasopressin does not result in sustained vasoconstriction, and this may limit the benefit of vasopressin in infusional chemotherapy. We have assessed whether loss of vasopressin-induced vasoconstriction is mediated by nitric oxide. Hepatic and tumour blood flow were continuously monitored, in an animal hepatic tumour model, by laser Doppler flowmetry. The response to regionally infused vasopressin and the nitric oxide inhibitor N-nitro-L-arginine methyl ester (L-NAME) were assessed over a 30 min infusion period. The vasopressin-induced vasoconstrictor effect diminished after 15 min despite continued infusion. Vasoconstriction was significantly prolonged when L-NAME was infused in addition to vasopressin. The increase in tumour to normal blood flow ratio was greater over the infusion period when L-NAME was co-administered with vasopressin. Our results suggest that the loss of vasopressin-induced vasoconstriction seen in liver parenchyma after regional infusion is prevented by the nitric oxide synthase inhibitor L-name and may be mediated by nitric oxide.
authors.affiliation: Department of Academic Surgery, Charing Cross and Westminster Medical School, Chelsea and Westminster Hospital, London, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Dworkin
authors.forename: P
authors.initials: P
authors.lastname: Carnochan
authors.forename: T G
authors.initials: TG
authors.lastname: Allen-Mersh
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006499:Hepatic Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000556:secondary; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D014667:Vasopressins; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester