Mechanisms of increased responses of the aorta to alpha-adrenoceptor agonists in streptozotocin-induced diabetic rats.
To investigate the influence of diabetes on the responsiveness of the cardiovascular system, we have examined the effects of various agents on the reactivity of the vascular smooth muscle of aortic strips obtained from age-matched control and diabetic rats. Norepinephrine (NE) contracted the aortic strips obtained from age-matched control and diabetic rats in a concentration-dependent manner, but maximal contraction of aortic strips in response to NE was enhanced in diabetic rats. The EC50 value for NE in the diabetic aortic strips was similar to that in the aorta from age-matched controls. Ca-induced contracture of the aortic strips which were depolarized with isotonic K+ (60 mM) was potentiated in aortic strips from diabetic rats, when compared with those from age-matched controls. Ca-induced contracture of aortic strips, preincubated with 10(-6) M NE and 10(-6) M nicardipine in Ca2+-free Krebs-Henseleit solution (KHS), was not significantly different in age-matched control and diabetic rats. Bay K 8644, an activator of calcium channels, produced an increase in the force of contraction of the slightly depolarized aorta from diabetic rats. Phasic contraction induced by phenylephrine (PE) in the presence of 10(-6) M nicardipine in Ca2+-free KHS was significantly enhanced in aortic strips obtained from diabetic rats. These results demonstrate that NE-induced contraction of the aortic strips obtained from diabetic rats was significantly enhanced, and that this increased contractile response of the aorta to NE may be due to an increased influx of extracellular calcium through the voltage-dependent Ca2+ channels, but not through the receptor-operated Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Kamata
K
K
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Miyata
N
N
Kasuya
Y
Y
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D015220:Calcium Channels; D010716:Phosphatidylinositols; D010656:Phenylephrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D009638:Norepinephrine