title: Diminishment of contractions associated with depolarization-evoked activation of Ca2+ channels in diabetic rat aorta.
abstract: Alterations in contractile responses of aortic rings mediated by activation of Ca2+ channels were investigated in rats with streptozotocin-induced diabetes. Eight to 12 weeks of diabetes resulted in a marked decrease in the contractile response of aortic rings to high K+. In contrast, diabetic aortas exhibited significantly greater contractions in response to noradrenaline compared to age-matched controls. In the presence of 15 mM K+, the Ca2+ channel agonist Bay K 8644 consistently produced 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 significant difference in basal 45Ca2+ uptake between control and diabetic aortas. However, the uptake of 45Ca2+ induced by high K+ was significantly less in diabetic aortas than in controls, and pretreatment with the Ca2+ channel antagonist nifedipine abolished both responses. The resting membrane potentials were not significantly different between control and diabetic aortas. Furthermore, no difference was found in the magnitude of depolarization evoked by increasing K+ concentrations between the two groups of tissues. There were no significant differences in the density and the dissociation constant for [3H]-(+)-PN200-110, a radiolabeled Ca2+ channel antagonist, between aortic membranes from control and diabetic rats. These data indicate that the contractile responses to high K+ and Bay K 8644 are specifically diminished in diabetic aortas. These diminished responses are not due to a difference in the number of Ca2+ channels, but may be related to an alteration in activation of the channels by membrane depolarization.
authors.affiliation: Department of Pharmacology, Hokkaido University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hattori
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: M
authors.initials: M
authors.lastname: Fukao
authors.forename: S
authors.initials: S
authors.lastname: Gando
authors.forename: Y
authors.initials: Y
authors.lastname: Akaishi
authors.forename: M
authors.initials: M
authors.lastname: Kanno
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine