Effects of clonidine‐induced hypotension and dopamine‐induced hypertension on blood flows in prostatic adenocarcinoma (dunning R3327) and normal tissues

Abstract

In the present study it was investigated whether hypertension induced by dopamine or hypotension induced by clonidine could influence the relative blood distribution in a s.c. transplanted prostatic adenocarcinoma in relation to blood flow in normal tissues in rats. The blood flow was measured by using a radioactive microspheres technique. A bolus injection of 5 micrograms clonidine caused a decrease in the systemic blood pressure with 15-45 mm Hg, and blood flow to the central parts of the tumor, decreased with more than 50%. In the prostate, testes and ileo-psoas muscle a similar reaction was seen. During an infusion of 95-120 micrograms/kg/min dopamine, the blood pressure increased with 15-30 mm Hg, but the blood flow to the tumor was unchanged. However, in the testes and kidneys a decreased blood flow was observed. Moreover, mean blood flow to the central parts of the tumor decreased with increase in tumor size. The results further indicated that hyper- or hypotension or concomitantly given vasoactive drugs with the specific cancer treatment can have unwarranted effects on the distribution of cytotoxic drugs and oxygenation of the tumor.

Vasomodulation of Tumor Blood Flow: Effect on Perfusion and Thermal Ablation Size

“…These techniques include the radioactive microsphere technique, 27 isotope (e.g. 85 Kr, 133 Xe) clearance, 11,31 uptake of radioactive tracer, 39 and the thermal clearance method.…”

Going malignant: the hypoxia‐cancer connection in the prostate

“…This in part is achieved through SREBP control of FAS-linked genes. (24,26) (22,23) despite probably higher perfusion (18,21) and HIF1-regulated, VEGF1-mediated hypertrophy of the microvasculature; (19,21) (2) an increased HIF1-induced glycolytic potential in malignant versus normal cells; (32,33) (3) cells being more reduced in normal prostate than in malignant prostate cells or in most other types of tissues (indicated by increases in Krebs cycle fluxes in malignancy which imply declines in the NADH/ NAD þ ratio); (4) roles for the transcription factors Sp1 and hypoxia-sensitive Sp3 (27,31) in regulation of genes involved in the metabolic transformation of normal to malignant prostate cells; (5) increasing amounts of HIF1 in malignant versus normal cells, (32,34) (6) increased hypoxia sensitization of HIF1a…”

“…(16,17) In the transformed state, blood flow is generally increased, the more advanced the tumor, the greater the blood flow appears to be. (18,19) Of course, increased angiogenesis may not necessarily lead to increased perfusion of malignant cells because of the formation of some abnormal vessels and arterio-venous shunts. Still, because of increased citrate oxidation, O 2 consumption rates are relatively increased, (6,7) but tissue pO 2 declines, (22,23) indicating that the elevation in energy demand in malignancy is not fully satisfied by adjusting blood flow and O 2 delivery.…”

“…In effect, a sluggish respiratory chain characterizes aerobic metabolism of the normal prostate, which indeed may be matched by a relatively modest microcirculation. (18)(19)(20)(21) Transforming the prostate metabolic phenotype during development of prostate cancer It is well known that in later stages of human prostate cancer and in animal models of prostate cancer, the above key biochemical characters change drastically (reviewed in Refs. [4][5][6][7][8][10][11][12].…”

Decrement of blood flow precedes the involution of the ventral prostate in the rat after castration

“…For tumor experiments, 18 Copenhagen X Fisher hybrid male rats of the same size and origin as the Sprague-Dawley rats, were implanted with a 1 x 1 mm piece of the transplantable cell line Dunning R3327-PAP, as previously described [21]. Some of the tumor bearing rats were castrated when the tumors had reached a size of approximately 1 cm 3.…”