Chronic ischemia alters prostate structure and reactivity in rabbits

Purpose: Autopsy studies performed in men older than 80 years old have demo nstrated that 90% have histological evidence of benign prostatic hyperplasi a. Despite this fact pressure flow studies in men of this age who are refer red for the evaluation of lower urinary tract symptoms have shown that only 40% have evidence of bladder outlet obstruction. To our knowledge the spec ific features of benign prostatic hyperplasia responsible for bladder outle t obstruction are not known. To investigate the possible etiological factor s responsible for bladder outlet obstruction we determined whether chronic ischemia alters the structural and functional properties of the prostate. Materials and Methods: Male New Zealand White rabbits weighing 3.5 to 4 kg. were divided into a chronic prostate ischemia (12), hypercholesterolemia ( 8) and age matched control (8) group. The chronic prostate ischemia group u nderwent balloon endothelial injury of the iliac arteries and received a 0. 5% cholesterol diet, the hypercholesterolemia group received a 0.5% cholest erol diet only and controls received a regular diet. After 12 weeks using a nesthesia iliac artery and prostatic blood now was measured by an ultrasoni c and laser Doppler flowmeter, respectively. The animals were then sacrific ed and the prostate was processed for histological evaluation, immunohistoc hemical staining for vascular endothelial growth factor expression and orga n bath studies. Results: Iliac artery and prostatic blood flow was significantly decreased in the chronic prostate ischemia compared with the hypercholesterolemia and control groups. Histological findings included thickening and fibrosis of the prostatic stroma and cystic atrophy of the epithelium in the chronic pr ostate ischemia group as well as minor thickening of the stroma in the hype rcholesterolemia group. These structural changes correlated with decreased vascular endothelial growth factor expression. Organ bath studies showed th at chronic ischemia and to a lesser extent hypercholesterolemia impaired el ectrical field stimulation induced neurogenic relaxation of the prostatic t issue. Neurogenic relaxation of the prostatic tissue was improved by combin ed treatment with indomethacin and L-arginine in the hypercholesterolemia b ut not in the chronic prostate ischemia group. Nitric oxide donor sodium ni troprusside produced comparable relaxation in all 3 groups. Conclusions: Chronic ischemia causes marked changes in prostatic structure and contractility. Ischemia induced glandular atrophy was consistently asso ciated with decreased vascular endothelial growth factor expression. Decrea sed relaxation of the ischemic tissue to electrical field stimulation appea rs to involve the nitric oxide pathway. The nitric oxide precursor L-argini ne reversed hypercholesterolemia induced impairment of prostatic tissue rel axation. Our study suggests that chronic ischemia results in thickening and fibrosis of the prostate, changing its mechanical properties. Chronic isch emia also impairs neurogenic relaxation in the prostate. We discuss the pos sible relationship of these changes to clinical bladder outlet obstruction.