DIMINISHMENT OF CONTRACTIONS ASSOCIATED WITH DEPOLARIZATION-EVOKED ACTIVATION OF CA2+ CHANNELS IN DIABETIC RAT AORTA

Alterations in contractile responses of aortic rings mediated by activ ation of Ca2+ channels were investigated in rats with streptozotocin-i nduced diabetes. Eight to 12 weeks of diabetes resulted in a marked de crease in the contractile response of aortic rings to high K+. In cont rast, diabetic aortas exhibited significantly greater contractions in response to noradrenaline compared to age-matched controls. In the pre sence of 15 mM K+, the Ca2+ channel agonist Bay K 8644 consistently pr oduced concentration-dependent contractions in control aortas. On the other hand, the half of diabetic aortas did not respond to Bay K 8644. As a result, the contractile response to Bay K 8644 was significantly less in diabetic aortas compared to controls. There was no significan t difference in basal Ca-45(2+) uptake between control and diabetic ao rtas. However, the uptake of Ca-45(2+) induced by high K+ was signific antly less in diabetic aortas than in controls, and pretreatment with the Ca2+ channel antagonist nifedipine abolished both responses. The r esting membrane potentials were not significantly different between co ntrol and diabetic aortas. Furthermore, no difference was found in the magnitude of depolarization evoked by increasing K+ concentrations be tween the two groups of tissues. There were no significant differences in the density and the dissociation constant for [H-3]-(+)-PN200-110, a radiolabeled Ca2+ channel antagonist, between aortic membranes from control and diabetic rats. These data indicate that the contractile r esponses to high K+ and Bay K 8644 are specifically diminished in diab etic aortas. These diminished responses are not due to a difference in the number of Ca2+ channels, but may be related to an alteration in a ctivation of the channels by membrane depolarization.