Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Sep;72(3):595–600. doi: 10.1038/bjc.1995.379

The response of tumour vasculature to angiotensin II revealed by its systemic and local administration to 'tissue-isolated' tumours.

G M Tozer 1, K M Shaffi 1
PMCID: PMC2033914  PMID: 7669567

Abstract

A tissue-isolated preparation of the P22 rat carcinosarcoma was used to investigate the tumour vascular response to angiotensin II (ATII). In particular, the relative importance of systemic and local tumour factors was assessed by comparing tumour vascular resistance during systemic administration of ATII and during administration directly into the tumour-supplying artery. The effect of hypervolaemia on tumour vascular resistance was determined as well as the effect of ATII on oxygen metabolism. Tumour vascular resistance was increased by ATII in a dose-dependent manner. The response was biphasic with an initial peak in resistance followed by a lower plateau phase. Systemic administration of ATII was more effective in increasing tumour vascular resistance than direct administration. This suggests that systemic administration is not causing any reopening of previously collapsed tumour blood vessels. Further evidence for this is that hypervolaemia caused no reduction in tumour vascular resistance and that there was no difference in oxygen extraction by tumours between groups treated with systemically and directly administered ATII. A heterogeneous distribution of ATII receptors in the P22 tumour is a more likely explanation for the known heterogeneity of blood flow response to ATII.

Full text

PDF
595

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson J. H., Willmott N., Bessent R., Angerson W. J., Kerr D. J., McArdle C. S. Regional chemotherapy for inoperable renal carcinoma: a method of targeting therapeutic microspheres to tumour. Br J Cancer. 1991 Aug;64(2):365–368. doi: 10.1038/bjc.1991.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Eskey C. J., Koretsky A. P., Domach M. M., Jain R. K. Role of oxygen vs. glucose in energy metabolism in a mammary carcinoma perfused ex vivo: direct measurement by 31P NMR. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2646–2650. doi: 10.1073/pnas.90.7.2646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. GRAY L. H., STEADMAN J. M. DETERMINATION OF THE OXYHAEMOGLOBIN DISSOCIATION CURVES FOR MOUSE AND RAT BLOOD. J Physiol. 1964 Dec;175:161–171. doi: 10.1113/jphysiol.1964.sp007509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. GULLINO P. M., GRANTHAM F. H. Studies on the exchange of fluids between host and tumor. I. A method for growing "tissue-isolated" tumors in laboratory animals. J Natl Cancer Inst. 1961 Sep;27:679–693. [PubMed] [Google Scholar]
  5. Graham R. A., Brown T. R., Meyer R. A. An ex vivo model for the study of tumor metabolism by nuclear magnetic resonance: characterization of the phosphorus-31 spectrum of the isolated perfused Morris hepatoma 7777. Cancer Res. 1991 Feb 1;51(3):841–849. [PubMed] [Google Scholar]
  6. Grantham F. H., Hill D. M., Gullino P. M. Primary mammary tumors connected to the host by a single artery and vein. J Natl Cancer Inst. 1973 May;50(5):1381–1383. doi: 10.1093/jnci/50.5.1381. [DOI] [PubMed] [Google Scholar]
  7. Gullino P. M. In vivo utilization of oxygen and glucose by neoplastic tissue. Adv Exp Med Biol. 1976;75:521–536. doi: 10.1007/978-1-4684-3273-2_62. [DOI] [PubMed] [Google Scholar]
  8. Hori K., Suzuki M., Tanda S., Saito S., Shinozaki M., Zhang Q. H. Fluctuations in tumor blood flow under normotension and the effect of angiotensin II-induced hypertension. Jpn J Cancer Res. 1991 Nov;82(11):1309–1316. doi: 10.1111/j.1349-7006.1991.tb01797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hori K., Zhang Q. H., Saito S., Tanda S., Li H. C., Suzuki M. Microvascular mechanisms of change in tumor blood flow due to angiotensin II, epinephrine, and methoxamine: a functional morphometric study. Cancer Res. 1993 Nov 15;53(22):5528–5534. [PubMed] [Google Scholar]
  10. Jirtle R., Clifton K. H., Rankin J. H. Effects of several vasoactive drugs on the vascular resistance of MT-W9B tumors in W/Fu rats. Cancer Res. 1978 Aug;38(8):2385–2390. [PubMed] [Google Scholar]
  11. Kerr D. J., Goldberg J. A., Anderson J. R., Wilmott N., Whatelely A. T., McArdle C. S., Mckillop J. The effect of angiotensin II on tumor blood flow and the delivery of microparticulate cytotoxic drugs. EXS. 1992;61:339–345. doi: 10.1007/978-3-0348-7001-6_55. [DOI] [PubMed] [Google Scholar]
  12. Kobayashi H., Hasuda K., Aoki K., Taniguchi S., Baba T. Systemic chemotherapy in tumor-bearing rats using high-dose cis-diamminedichloroplatinum(II) with low nephrotoxicity in combination with angiotensin II and sodium thiosulfate. Int J Cancer. 1990 May 15;45(5):940–944. doi: 10.1002/ijc.2910450527. [DOI] [PubMed] [Google Scholar]
  13. Kobayashi H., Hasuda K., Taniguchi S., Baba T. Therapeutic efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with the angiotensin-II-induced hypertension method in a rat uterine tumor. Int J Cancer. 1991 Apr 1;47(6):893–898. doi: 10.1002/ijc.2910470618. [DOI] [PubMed] [Google Scholar]
  14. Mutoh S., Aikou I., Soejima K., Ueda S., Fukushima S., Kishimoto S., Takagi Y. Local control of prostate cancer by intraarterial infusion chemotherapy facilitated by the use of angiotensin II. Urol Int. 1992;48(2):175–180. doi: 10.1159/000282325. [DOI] [PubMed] [Google Scholar]
  15. Noguchi S., Miyauchi K., Nishizawa Y., Sasaki Y., Imaoka S., Iwanaga T., Koyama H., Terasawa T. Augmentation of anticancer effect with angiotensin II in intraarterial infusion chemotherapy for breast carcinoma. Cancer. 1988 Aug 1;62(3):467–473. doi: 10.1002/1097-0142(19880801)62:3<467::aid-cncr2820620304>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  16. Phillips M. I. Functions of angiotensin in the central nervous system. Annu Rev Physiol. 1987;49:413–435. doi: 10.1146/annurev.ph.49.030187.002213. [DOI] [PubMed] [Google Scholar]
  17. Pörsti I., Hecker M., Bassenge E., Busse R. Dual action of angiotensin II on coronary resistance in the isolated perfused rabbit heart. Naunyn Schmiedebergs Arch Pharmacol. 1993 Dec;348(6):650–658. doi: 10.1007/BF00167243. [DOI] [PubMed] [Google Scholar]
  18. Sensky P. L., Prise V. E., Tozer G. M., Shaffi K. M., Hirst D. G. Resistance to flow through tissue-isolated transplanted rat tumours located in two different sites. Br J Cancer. 1993 Jun;67(6):1337–1341. doi: 10.1038/bjc.1993.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sevick E. M., Jain R. K. Geometric resistance to blood flow in solid tumors perfused ex vivo: effects of tumor size and perfusion pressure. Cancer Res. 1989 Jul 1;49(13):3506–3512. [PubMed] [Google Scholar]
  20. Sevick E. M., Jain R. K. Measurement of capillary filtration coefficient in a solid tumor. Cancer Res. 1991 Feb 15;51(4):1352–1355. [PubMed] [Google Scholar]
  21. Sevick E. M., Jain R. K. Viscous resistance to blood flow in solid tumors: effect of hematocrit on intratumor blood viscosity. Cancer Res. 1989 Jul 1;49(13):3513–3519. [PubMed] [Google Scholar]
  22. Suzuki M., Hori K., Abe I., Saito S., Sato H. A new approach to cancer chemotherapy: selective enhancement of tumor blood flow with angiotensin II. J Natl Cancer Inst. 1981 Sep;67(3):663–669. [PubMed] [Google Scholar]
  23. Takematsu H., Tomita Y., Kato T. Angiotensin-induced hypertension and chemotherapy for multiple lesions of malignant melanoma. Br J Dermatol. 1985 Oct;113(4):463–465. doi: 10.1111/j.1365-2133.1985.tb02361.x. [DOI] [PubMed] [Google Scholar]
  24. Tanda S., Hori K., Saito S., Shinozaki M., Zhang Q. H., Suzuki M. Comparison of the effects of intravenously bolus-administered endothelin-1 and infused angiotensin II on the subcutaneous tumor blood flow in anesthetized rats. Jpn J Cancer Res. 1991 Aug;82(8):958–963. doi: 10.1111/j.1349-7006.1991.tb01927.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tokuda K., Abe H., Aida T., Sugimoto S., Kaneko S. Modification of tumor blood flow and enhancement of therapeutic effect of ACNU on experimental rat gliomas with angiotensin II. J Neurooncol. 1990 Jun;8(3):205–212. doi: 10.1007/BF00177353. [DOI] [PubMed] [Google Scholar]
  26. Tozer G. M., Shaffi K. M. Modification of tumour blood flow using the hypertensive agent, angiotensin II. Br J Cancer. 1993 May;67(5):981–988. doi: 10.1038/bjc.1993.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tozer G. M., Shaffi K. M., Prise V. E., Cunningham V. J. Characterisation of tumour blood flow using a 'tissue-isolated' preparation. Br J Cancer. 1994 Dec;70(6):1040–1046. doi: 10.1038/bjc.1994.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Trotter M. J., Chaplin D. J., Olive P. L. Effect of angiotensin II on intermittent tumour blood flow and acute hypoxia in the murine SCCVII carcinoma. Eur J Cancer. 1991;27(7):887–893. doi: 10.1016/0277-5379(91)90140-9. [DOI] [PubMed] [Google Scholar]
  29. Tveit E., Weiss L., Lundstam S., Hultborn R. Perfusion characteristics and norepinephrine reactivity of human renal carcinoma. Cancer Res. 1987 Sep 1;47(17):4709–4713. [PubMed] [Google Scholar]
  30. Vaupel P., Fortmeyer H. P., Runkel S., Kallinowski F. Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. Cancer Res. 1987 Jul 1;47(13):3496–3503. [PubMed] [Google Scholar]
  31. Vaupel P., Kallinowski F., Dave S., Gabbert H., Bastert G. Human mammary carcinomas in nude rats--a new approach for investigating oxygen transport and substrate utilization in tumor tissues. Adv Exp Med Biol. 1985;191:737–751. doi: 10.1007/978-1-4684-3291-6_75. [DOI] [PubMed] [Google Scholar]
  32. Weiss L., Tveit E., Jansson I., Hultborn R. Vascular reactivity to norepinephrine of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and normal tissue as studied in vitro. Cancer Res. 1986 Jul;46(7):3254–3257. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES