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International Angiology 2000 March;19(1):52-8


lingua: Inglese

Decreased binding sites of angiotensin II in rat LY-80 and AH109A tumour and human gastric cancer using quantitative in vitro autoradiography

Kohzuki M., Tanda S., Hori K., Susuki M., Yoshida K., Sato T.

Section of Internal Medicine & Disability Prevention and * Institute of Development, Aging and Cancer, Tohoku University Graduate School of Medicine, Sendai, Japan


Background. Under system­ic hyper­ten­sion ­induced by angio­ten­sin II (AII) infu­sion, an atten­u­at­ed vas­o­con­stric­tive ­response to the infu­sion in ­tumours was ­observed and a ­marked ­increase in ­tumour blood flow was ­observed in com­par­i­son with that in nor­mal tis­sues. The ­results show a par­allel cir­cuit that con­nects the vas­cu­lar bed of the pre-exist­ing tis­sue to that of the ­tumour. The phe­nom­e­non was ­absent when hyper­ten­sion was pro­voked by other vas­o­con­stric­tive ­agents such as nor­epi­neph­rine or endo­the­lin-1. However, the bio­log­i­cal basis for this atten­u­at­ed vas­o­con­stric­tive ­response to angio­ten­sin II ­observed in ­tumours has not been fully elu­ci­dat­ed.
Methods. We ­assessed this ­response to char­ac­ter­ise the angio­ten­sin II recep­tor den­sity and affin­ity in nor­mal and ­tumour tis­sues. AH109A and LY80 ­tumour cell lines were trans­plant­ed to the skin in nude rats. Four weeks later, the rats were sac­ri­ficed. 125I-[Sar1, Ile8] angio­ten­sin II was used to map its recep­tors in rat tis­sues using
in vitro com­pu­ter­ised auto­ra­diog­ra­phy. Operated human gas­tric can­cer tis­sues from a 49-year-old and a 66-year-old male ­patients were also inves­ti­gat­ed.
Results. The num­bers of angio­ten­sin II recep­tors were mark­ed­ly ­reduced in ­tumour tis­sues with­out a ­change of affin­ity. The num­bers in AII-R in ­tumours were shown to be main­ly AT1 by the ­marked reduc­tion in radio­lig­and bind­ing ­achieved by losar­tan but not by PD123177. The same ­results were ­observed in human gas­tric can­cer.
Conclusions. These ­results sug­gest that the ­decrease in angio­ten­sin II recep­tors in ­tumours may ­explain the hae­mod­y­nam­ic ­effect of angio­ten­sin II-­induced hyper­ten­sion on ­tumour blood flow. This con­di­tion for drug deliv­ery to ­tumour tis­sue may play a major role in enhanc­ing the ther­a­peu­tic ­effects of chem­o­ther­a­py.

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