INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
INTRODUCTION: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- dihydropyridinecalcium channel blocker (Nifedipine). In this study, we examined dual calcium channel blocking and AT1 antagonist activity for DHPEE. METHODS: 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. RESULTS: 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. CONCLUSION: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.
Authors: Kee Hun Do; Min Sung Kim; Jae Ho Kim; Byung Yong Rhim; Won Suk Lee; Chi Dae Kim; Sun Sik Bae Journal: Exp Mol Med Date: 2009-08-31 Impact factor: 8.718