Vascular contraction induced by activation of membrane calcium ion channels is enhanced in streptozotocin-diabetes.
Previous results from our laboratory (White and Carrier, Enhanced Vascular Alpha-Adrenergic Neuroeffector System in Diabetes: Importance of Calcium. Am. J. Physiol. 255: H1036-1042, 1988) demonstrated that mesenteric arteries from streptozotocin (STZ)-diabetic rats exhibit an enhanced responsiveness to alpha adrenergic agonists. The present study demonstrates that this enhanced responsiveness is dependent upon the presence of extracellular calcium. Arteries from STZ-diabetic (10-12 weeks) rats developed greater contractile force in response to norepinephrine or KCl. Development of these effects was prevented by daily insulin treatment, indicating these alterations are related to the diabetic state. Similarly, the contractile response to extracellular calcium in the presence of norepinephrine (3 x 10(-6) M) or KCl (60 mM) was greater in arteries from STZ-diabetic animals. BAY K 8644, a calcium channel agonist, induced greater contraction in arteries from STZ-diabetic animals, as did activation of protein kinase C by phorbol dibutyrate. In contrast, contraction induced by release of calcium from intracellular sources (alpha-1 adrenoceptor-mediated or caffeine-induced) was unaltered by diabetes. These findings indicate that enhanced vascular contraction in STZ-diabetes is of a nonspecific nature, i.e., the contractile response to any agent which induces extracellular calcium-dependent contraction should be enhanced in diabetes. We propose that STZ-diabetes enhances the activity and/or number of calcium ion channels in vascular smooth muscle.
Department of Pharmacology & Toxicology, Medical College of Georgia, Augusta.
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White
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Carrier
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D015220:Calcium Channels; 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