Effect of exercise on augmented aortic vasoconstriction in the db/db mouse model of type-II diabetes

We evaluated the effects of exercise on the vascular constrictorresponses to α-adrenergic stimulation in the db/db mice. Twentymale db/db and their age-matched wild-type (WT) mice wereexercised (1 hour/day, five days a week). Mice were anesthetized7 weeks later, thoracic aortae were mounted in wire myographand constrictor responses to phenylephrine (PE, 1 nM-10 μM)were obtained. Citrate synthase activity measured in the thighadductor muscle was significantly increased in db/db mice thatwere exercise trained. Maximal force generated by PE wasmarkedly greater in db/db aortae and exercise did not attenuatethis augmented contractile response. Vessels were incubatedwith inhibitors of nitric oxide synthase (L-NAME, 200 μM),endothelin receptors (bosentan, 10 μM), protein kinase C (PKC)(calphostin C, 5 μM), cyclooxygenase (indomethacin, 10 μM) orRho-kinase (Y-27632, 0.1 μM). Only calphostin-C normalized theaugmented PE-induced constriction in db/db and db/dbexercised mice to that observed in WT (p<0.05). Cumulative additions of indolactam, a PKC activator, induced significantly greater constrictor responses in aortic rings of db/db micecompared to WT and exercise did not affect this response. Ourdata suggest that the augmented vasoconstriction observed inthe aorta of db/db mice is likely due to increased PKC activity andthat exercise do not ameliorate this increased PKC-mediatedvasoconstriction.