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 constrictor responses to alpha-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 anesthetized 7 weeks later, thoracic aortae were mounted in wire myograph and constrictor responses to phenylephrine (PE, 1 nM-10 microM) were 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, 200 microM), endothelin receptors (bosentan, 10 microM), protein kinase C (PKC) (calphostin C, 5 microM), cyclooxygenase (indomethacin, 10 microM) or Rho-kinase (Y-27632, 0.1 microM). 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 mice compared to WT and exercise did not affect this response. Our data suggest that the augmented vasoconstriction observed in the aorta of db/db mice is likely due to increased PKC activity and that exercise do not ameliorate this increased PKC-mediated vasoconstriction.
Department of Physiology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
M
M
Khazaei
F
F
Moien-Afshari
T J
TJ
Kieffer
I
I
Laher
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002950:Citrate (si)-Synthase / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005082:Physical Exertion; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D065130:Endothelin A Receptor Antagonists; D020536:Enzyme Activators; D007328:Insulin; D008055:Lipids; D047428:Protein Kinase Inhibitors; D044022:Receptor, Endothelin A; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D002950:Citrate (si)-Synthase; D054460:rho-Associated Kinases; D011493:Protein Kinase C