Role of extracellular Ca2+ in the selective enhancement of contractile responses of arteries from diabetic rats to noradrenaline.
Maximum contractile responses of diabetic aortas incubated in the absence of extracellular Ca2+ to increasing Ca2+ (0.01-10 mM) in the presence of 1 microM noradrenaline, but not 40 mM KCl, were significantly increased compared with those of age-matched control rats. Maximum contractile responses of both aortas and mesenteric arteries from diabetic rats to noradrenaline, but not KCl, in the presence of extracellular Ca2+ (2.5 mM) were also significantly enhanced. The Ca2+ channel antagonists verapamil and nifedipine and the Ca2+ channel agonist BAY K8644 produced a similar percentage change in the magnitude of the noradrenaline response in arteries from both control and diabetic rats. These data confirm the selective nature of the enhancement of contractile responses of arteries from diabetic rats to noradrenaline and suggest that this may be mediated in part through enhanced noradrenaline-induced influx of extracellular Ca2+ through channels sensitive to the Ca2+ channel ligands. However, this does not appear to be the only explanation for the enhanced contractile responses of diabetic arteries to noradrenaline, since in the presence of maximum concentrations of nifedipine (3 microM) and verapamil (10 microM), responses of diabetic arteries to noradrenaline were still greater than those of control arteries.
Abebe
W
W
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Harris
K H
KH
MacLeod
K M
KM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D009638:Norepinephrine