Hypotensive Effect of a Novel Dihydropyridine with Dual Calcium Channel Blocking and Angiotensin II Antagonistic Properties in a Rat Model

In our previous work, we synthesized a novel analogue of losartan (Compound A) with dual calcium (Ca2+) channel blocking andantagonism of angiotensin II (ANG II) type 1 receptor (AT1) activity. In this study, the effects of this compound (compound A) on the blood pressure (BP) and the heart rate (HR) of normotensive rats were investigated and compared to losartan, which was used as a positive control. A novel dihydropyridine compound was synthesized by connecting a dihydropyridine nucleus to an imidazole ring. Three doses of compound A (0.25, 0.5 and 1 mg/kg) and three doses of losartan (1, 2 and 4 mg/kg) were administered intravenously to different groups of normotensive male rats, and their effects on mean arterial BP (MABP) and heart rate (HR) were evaluated. All three doses of compound A reduced the MABP in normotensive anaesthetized rats in a dose-dependent manner. The administration of 1 mg/kg of compound A and 4 mg/kg of losartan (the largest doses) caused a reduction of 67.2 ± 2.2 and 69.3 ± 2.9 mmHg in the MABP, respectively. It can be concluded that like losartan, compound A has hypotensive properties. It can also be concluded that compound A has greater potency than losartan.