Contractile responses of diabetic rat aorta to phenylephrine at different stages of diabetic duration.
OBJECTIVE
To investigate the time-dependent changes in contractile responses of aorta to phenylephrine (Phe) in diabetic rats and age-matched control, and its possible mechanism.


METHODS
At stages of 2-, 6-, and 12-week diabetic duration, aortic rings were studied for contractile responses to agonists in vitro.


RESULTS
At the stage of 2-week diabetic duration, contractile responses to lower concentrations of phenylephrine were increased (P < 0.05), but the maximal contraction of phenylephrine did not change. At the stage of 6-week diabetic duration, contractile responses to phenylephrine were increased (P < 0.01) at each concentration, and the maximal contraction was increased by approximately 40 %. However, at the stage of 12-week diabetic duration: 1) the maximal contractile response to Phe 10 micromol . L-1 was decreased (P < 0.05), 2) in Ca2+ free edetic acid medium, Phe 10 micromol . L-1-induced transient contraction was also decreased (P < 0.05), 3) in Ca2+ free edetic acid medium, in the presence of nifedipine 10 micromol . L-1 and Phe 10 micromol . L-1, the Ca2+ repletion-caused contraction was not different from control, 4) in normal medium, cyclopiazonic acid (CPA) 10 micromol . L-1-induced contraction was decreased (P < 0.01).


CONCLUSIONS
The results suggested that contractile responses to phenylephrine in diabetic rat aorta changed with the development of diabetes, and the changes of functional Ca2+ store sizes and Ca2+ entry mainly through voltage-dependent Ca2+ channels were responsible for the alterations of contractile responses to phenylephrine in diabetes.
Zhu
B H
BH
Department of Pharmacology, Sun Yat-Sen University of Medical Sciences, Guangzhou 510089, China. sszhu@gzsums.edu.cn
Guan
Y Y
YY
Min
J
J
He
H
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D015220:Calcium Channels; D007211:Indoles; D010656:Phenylephrine; D002118:Calcium; C000543:cyclopiazonic acid