Effect of Exercise on Augmented Aortic Vasoconstriction in the Db/Db Mouse Model of Type-Ii Diabetes Pubmed



Khazaei M¹ ; Moienafshari F² ; Kieffer TJ³ ; Laher I² Show Affiliations
Source: Physiological Research Published:2008

Abstract

We evaluated the effects of exercise on the vascular constrictor responses to α-adrenergic stimulation in the db/db mice. Twenty male db/db and their age-matched wild-type (WT) mice were exercised (1 hour/day, five days a week). Mice were anaesthetized 7 weeks later and thoracic aortae mounted in wire myograph and constrictor responses to phenylephrine (PE, 1 nM-10μM) obtained. Citrate synthase activity measured in the thigh adductor muscle was significantly increased in db/db mice that were exercise trained. Maximal force generated by PE was markedly greater in db/db aortae and exercise did not attenuate this augmented contractile response. Vessels were incubated with inhibitors of nitric oxide synthase (L-NAME, 200μM), endothelin receptors (bosentan, 10 μM), protein kinase C (PKC) (calphostin C, 5μM), cyclooxygenase (indomethacin, 10μM) or Rho-kinase (Y-27632, 0.1μM). Only calphostin-C normalized the augmented PE-induced constriction in db/db and db/db- exercised 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 compared to WT and exercise did not affect this response. Data suggest that the augmented vasoconstriction observed in the aorta of db/db mice is likely due to increased PKC activity and that exercise don't ameliorate this increased PKC-mediated vasoconstriction.