ALTERATIONS OF MITOCHONDRIAL OXIDATIVE-METABOLISM IN RABBIT URINARY-BLADDER AFTER PARTIAL OUTLET OBSTRUCTION

Previous studies demonstrated that one of the most significant cellula r responses of the rabbit urinary bladder to partial outlet obstructio n is a 50% decrease in the activities of the mitochondrial enzymes cit rate synthase and malate dehydrogenase, when calculated as either acti vity per unit mass or activity per mg protein. A major question arose from these studies: Are the mitochondrial enzyme activities per mitoch ondrion reduced, or is the number of mitochondria per unit tissue mass reduced? The current experiments were designed to study the sequentia l changes in the activities of mitochondrial oxidative enzymes followi ng partial outlet obstruction. The activities of NADH-cytochrome c red uctase (NCCR), cytochrome oxidase (CO), citrate synthase (CS) and mala te dehydrogenase (MDH) were measured in whole tissue homogenates and i n mitochondrial preparations of separated bladder mucosa and muscle, f rom normal bladders, and, from hypertrophied bladders at 1, 3, and 7 d ays following partial outlet obstruction. The results can be summarize d as follows: 1) Whole tissue homogenates: Activities of all enzymes w ere reduced to approximately 50% of control at 1 day following partial outlet obstruction. NCCR and CO activities returned to 75 and 85% of control respectively by 7 days post-obstruction; CS activity did not s how any significant recovery over the 7 day period. 2) Mucosal and smo oth muscle mitochondrial preparations: Activities of all enzymes were decreased significantly by 50% or greater at 1 day following partial o utlet obstruction. The cytochrome (NCCR and CO) enzyme activities retu rned to control levels by 7 days post-obstruction; CS activity showed only a minor recovery over this time period. These results show that m itochondrial enzyme activity is significantly impaired immediately fol lowing partial outlet outlet obstruction, and whereas the activity of the cytochrome enzymes NCCR and CO recover to control levels (in the m itochondrial preparations) within 7 days post obstruction, the Krebs c ycle enzymes (CS and MD) show no significant recovery. Thus, the regul atory mechanisms for the cytochromes is significantly different from t hat for the enzymes of the krebs cycle.