B H Zhu1, Y Y Guan, J Min, H He. 1. Department of Pharmacology, Sun Yat-Sen University of Medical Sciences, Guangzhou 510089, China. sszhu@gzsums.edu.cn
Abstract
AIM: 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). CONCLUSION: 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.
AIM: To investigate the time-dependent changes in contractile responses of aorta to phenylephrine (Phe) in diabeticrats 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). CONCLUSION: The results suggested that contractile responses to phenylephrine in diabeticrat 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.
Authors: Cini Mathew John; Rayan Khaddaj Mallat; Ramesh C Mishra; Grace George; Vikrant Singh; Jeannine D Turnbull; Channakeshava S Umeshappa; Dylan J Kendrick; Taeyeob Kim; Fazlin M Fauzi; Frank Visser; Paul W M Fedak; Heike Wulff; Andrew P Braun Journal: Pharmacol Res Date: 2019-11-07 Impact factor: 7.658
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