Synthesis and Effects of Novel Dihydropyridines as Dual Calcium Channel Blocker and Angiotensin Antagonist on Isolated Rat Aorta

Objective(s) Four novel losartan analogues ۵a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of ۵a and ۵b on angiotensin receptors (AT') and L-type calcium channels were investigated on isolated rat aorta. Materials and Methods Aortic rings were pre-contracted with ۱ pM Angiotensin II or ۸۰ mM KCl and relaxant effects of losartan, nifedipine, ۵a and ۵b were evaluated by cumulative addition of these drugs to the bath solution. Results The results showed that compounds ۵a and ۵b have both L-type calcium channel and AT' receptor blocking activity. Their effects on AT' receptors are ۱۰۰۰ and ۱۰۰,۰۰۰ times more than losartan respectively. The activity of compound ۵b on L-type calcium channel is significantly less than nifedipine but compound ۵a has comparable effect with nifedipine. Conclusion Finally we concluded that these two new Compounds can be potential candidates to be used as effective antihypertensive agents.

Keywords:

Angiotensin , aorta , Dihydropyridine