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

Background. Under systemic hypertension induced by angiotensin II (AII) inf usion, an attenuated vasoconstrictive response to the infusion in tumours w as observed and a marked increase in tumour blood flow was observed in comp arison with that in normal tissues. The results show a parallel circuit tha t connects the vascular bed of the pre-existing tissue to that of the tumou r. The phenomenon was absent when hypertension was provoked by other vasoco nstrictive agents such as norepinephrine or endothelin-1. However, the biol ogical basis for this attenuated vasoconstrictive response to angiotensin I I observed in tumours has not been fully elucidated. Methods. We assessed this response to characterise the angiotensin II recep tor density and affinity in normal and tumour tissues. AH109A and LY80 tumo ur cell lines were transplanted to the skin in nude rats. Four weeks later, the rats were sacrificed. I-125-[Sar1, Ile(8)] angiotensin II was used to map its receptors in rat tissues using in vitro computerised autoradiograph y. Operated human gastric cancer tissues from a 49-year-old and a 66-year-o ld male patients were also investigated. Results. The numbers of angiotensin II receptors were markedly reduced in t umour tissues without a change of affinity. The numbers in AII-R in tumours were shown to be mainly ATI by the marked reduction in radioligand binding achieved by losartan but not by PD123177. The same results were observed i n human gastric cancer. Conclusions. These results suggest that the decrease in angiotensin II rece ptors in tumours may explain the haemodynamic effect of angiotensin II-indu ced 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.