اثرات قلبی– عروقی سه ترکیب صناعی جدید مهارکننده کانال‌های کلسیمی در خرگوش

Background: Calcium channel blockers are important group of drugs that have been used in the treatment of a variety of cardiovascular diseases especially hypertension. In this study we have investigated the effects of three newly synthetized ester analogs of nifedipine (Compounds No. 1, 2 and 3) compared to nifedipine on mean arterial pressure, dp/dt (cardiac contractility index) and heart rate in rabbits. Materials and Methods: This study was carried out on 24 white New Zealand rabbits in three groups. Rabbits were anaesthetized with diazepam and sodium pentobarbital. The right femoral vein and artery were cannulated for injections (phenylephrin and sodium pentobarbital) and record of arterial blood pressure respectively. Right jugular vein was cannulated for injection of synthetic compounds. Another cannula was inserted in right carotid artery and pushed slowly to left ventricle to record the left ventricular dp/dt as a measure of cardiac contractility. Then the new compounds were tested in two stages. In the first stage during normotensive conditions, 1ml nifedipine (10-4 M) and five minutes later 1ml of the new compounds were injected through the jugular vein during 1 minute and their effect on arterial blood pressure and left ventricular dp/dt was recorded. Twenty minutes later when arterial blood pressure returned to basal level, 1ml of 10-3 M nifedipine and each of the synthetic compounds were injected. In the second stage, arterial blood pressure was increased by 20 mmHg with continuous phenylephrin infusion and then the first stage experiments were repeated in hypertensive conditions. &rlm;Results:The results showed that in hypertensive conditions, 10-3 M of nifedipine reduced the mean arterial pressure (MAP) and dp/dt by 22.1%, and 19.7% respectively, and increased the heart rate (HR) by 4.8%. Compound 1 reduced MAP by 7.5%, and dp/dt by 8.3% but had no effect on HR. Compound 2 (10-3 M), reduced MAP, and dp/dt by 9% and 11.2% respectively, but had no effect on HR. Compound 3 decreased 10.2% MAP, and 7.6% dp/dt and increased HR by 1.4%. Compounds 1 and 2 significantly reduced heart rate compared with nifidipine (P<0.05). All three compounds with the concentration of 10-4 M had lower effect than nifedipine. Conclusion: Overall this study showed that compound 2 is closer to nifedipine in reducing MAP and dp/dt, but does not increase HR. Although its lowering effect on BP is less than nifedipine, it may be selected for further investigation to increase its antihypertensive effect and probable side effects. Then it may be used in hypertensive patients with ischemic heart disease as it does not increase HR and O2 consumption. Keywords: Calcium Channel Blockers, New Dihydropyridine Derivatives, Hypertension, Cardiac Contractility, Heart Rate. *Corresponding author: Email najafipourh@ kmu.ac.ir, tel: (0341)3221661-4 Journal of Rafsanjan University of Medical Sciences and Health Services, 2002, 2(1): 10-21