title: Modulation of blood flow, hypoxia, and vascular function in orthotopic prostate tumors during exercise.
abstract: BACKGROUND
  Previous studies have hypothesized that tumor blood flow may be elevated or reduced during exercise, which could impact the tumor microenvironment. However, to date technical limitations have precluded the measurement of tumor blood flow during exercise. Using an orthotopic preclinical model of prostate cancer, we tested the hypotheses that during exercise tumors would experience 1) diminished vascular resistance, 2) augmented blood flow, 3) increased numbers of perfused vessels, and 4) decreased tissue hypoxia and, furthermore, that the increased perfusion would be associated with diminished vasoconstriction in prostate tumor arterioles.
  
  
  METHODS
  Dunning R-3327 MatLyLu tumor cells were injected into the ventral prostate of male Copenhagen rats aged 4 to 6 months randomly assigned to tumor-bearing (n = 42) or vehicle control (n = 14) groups. Prostate tumor blood flow, vascular resistance, patent vessel number, and hypoxia were measured in vivo in conscious rats at rest and during treadmill exercise, and vasoconstrictor responsiveness of resistance arterioles was investigated in vitro.
  
  
  RESULTS
  During exercise there was a statistically significant increase in tumor blood flow (approximately 200%) and number of patent vessels (rest mean ± standard deviation [SD] = 12.7±1.3; exercise mean ± SD = 14.3±0.6 vessels/field; Student t test two-sided P = .02) and decreased hypoxia compared with measurements made at rest. In tumor arterioles, the maximal constriction elicited by norepinephrine was blunted by approximately 95% vs control prostate vessels.
  
  
  CONCLUSIONS
  During exercise there is enhanced tumor perfusion and diminished tumor hypoxia due, in part, to a diminished vasoconstriction. The clinical relevance of these findings are that exercise may enhance the delivery of tumor-targeting drugs as well as attenuate the hypoxic microenvironment within a tumor and lead to a less aggressive phenotype.
authors.affiliation: Affiliations of authors: Department of Applied Physiology, University of Florida, Gainesville, FL (DJM, JNS, BJB); Department of Radiation Oncology, University of Florida Shands Cancer Center, Gainesville, FL (DWS); Experimental Therapeutics, University of Florida Health Cancer Center, Gainesville, FL (DWS, BJB).
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: McCullough
authors.forename: John N
authors.initials: JN
authors.lastname: Stabley
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Siemann
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Behnke
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D005082:Physical Exertion; D011471:Prostatic Neoplasms / Q000098:blood supply*; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D014662:Vasoconstrictor Agents; D009638:Norepinephrine