Babaei Hossein, Ebrahimi Farzaneh, Shahbazi Mojarrad Javid, Azarmi Yadollah, Gharehbagheri Afsaneh
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ; School of Pharmacy, Pharmacology Department, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2011;1(1):10-7. doi: 10.5681/apb.2011.002. Epub 2011 Jul 20.
DHPEE is a newly synthesized compound by merging the key structural elements in an angiotensin receptor blocker (Telmisartan) with key structural elements in 1,4- dihydropyridine calcium channel blocker (Nifedipine). In this study, we examined dual calcium channel blocking and AT1 antagonist activity for DHPEE.
The functional inhibitory characteristics of DHPEE were studied in vitro in rat thoracic aorta preparations precontracted by phenylephrine (1μM) or KCl (80μM) or Ang II in normal or calcium-free solutions.
Concentration-dependent significant relaxation was observed in aortic rings precontracted with phenylephrine, KCl or Ang II. The tension increment produced by increasing external calcium was also reduced by DHPEE. DHPEE caused a marked decrease in the maximal contractile response of the vasoactive agents and shifted their concentration-response curves to the right.
DHPEE possesses dual characteristics and cause vasorelaxation by blocking the L-type calcium channels and blocking Ang II receptors (AT1) in rat aortic smooth muscle.
DHPEE是一种新合成的化合物，它将血管紧张素受体阻滞剂（替米沙坦）的关键结构元素与1,4-二氢吡啶类钙通道阻滞剂（硝苯地平）的关键结构元素结合在一起。在本研究中，我们检测了DHPEE的双重钙通道阻断和AT1拮抗剂活性。
在体外，对用去氧肾上腺素（1μM）、氯化钾（80μM）或血管紧张素II预收缩的大鼠胸主动脉标本，在正常或无钙溶液中研究DHPEE的功能抑制特性。
在用去氧肾上腺素、氯化钾或血管紧张素II预收缩的主动脉环中观察到浓度依赖性的显著舒张。增加细胞外钙所产生的张力增加也被DHPEE降低。DHPEE使血管活性药物的最大收缩反应显著降低，并使其浓度-反应曲线右移。
DHPEE具有双重特性，通过阻断大鼠主动脉平滑肌中的L型钙通道和阻断血管紧张素II受体（AT1）引起血管舒张。
