Role of vascular dysfunction in prostate tumor perfusion during exercise

Abstract

During exercise, blood flow to inactive tissues is reduced through changes in vascular tone elicited largely by the autonomic nervous system. However, in tumors the reduced innervation of feed arteries and possibly blunted adrenergic vasoconstriction may lead to an increased tumor perfusion during exercise. We used control (CON; n=16) and prostate tumor bearing (TB; n=14) Copenhagen rats to test the hypothesis that α‐adrenergic (via norepinephrine; NE) and myogenic vasoconstrictor responses are diminished in the prostatic tumor feed arteries (PTA), resulting in an increased tumor perfusion during exercise. Dunning R‐3327 MatLyLu tumor cells (104) were injected into the ventral prostates of rats. PTA and prostate arteries (CON) were studied in vitro and exposed to cumulative additions of NE (10−9to 10−4M) and increases in intraluminal pressure (myogenic response; 0 to 135 cmH2O). In vivo quantification of perfused tumor vessels during rest and acute exercise (treadmill; 5 min) was determined using Hoechst‐33342 staining. Both α‐adrenergic (7 ± 6% vs. 88 ± 2%, p<0.05) and myogenic vasoconstriction were blunted in PTA versus CON, while the number of PTA perfused increased ~113% with exercise. These data suggest that dysfunction in the PTA results in an inability to augment vascular resistance during exercise, resulting in an enhanced tumor perfusion.Supp.: NIH (AG‐31317) & Florida Biomed. Res. Prog. (1BN‐02).