Central effects of synthesized dihydropyridine derivatives and nifedipine on systolic blood pressure and heart rate of rats
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Background: Calcium channel blockers have an important role in treatment of various cardiovascular diseases including hypertension, angina pectoris and cardiac arrhythmias, so study of cardiovascular effects of derivatives of these drugs are useful. Nifedipine is one of these drugs that used widely to treat hypertension and other cardiovascular diseases. The aim of the present study was to evaluate the central effects of synthesized dihydropyridine derivatives on systolic blood pressure and heart rate of rats and comparison to nifedipine. Methods: Sixty four male rats, after induction of anesthesia and intracerebral ventricular cannulation using stereotaxis method, were divided into eight equal groups. One week after the stereotaxis surgery, the systolic blood pressure and heart rate were evaluated in times 15 to 60 minutes after intracerebral ventricular injection of DMSO (dimethylsulfoxide) and nifedipine in doses of 80 to 320 microgram/rat and also three synthesized dihydropyridine derivatives (A, B and C) in dose of 240 microgram/rat. Effects of these drugs on systolic blood pressure and heart rate were analyzed using two way repeated measure ANOVA statistical test, followed by Bonferroni posthoc test. All data were considered significant at P < 0.05. Results: The inhibitory effects of derivative B on systolic blood pressure and heart rate in dose of 240 microgram/rat in times of 15 and 30 minutes after injection were more potent than nifedipine (P < 0.001), while A and C derivatives showed weaker inhibitory properties, compared with nifedipine. Also the inhibitory effects of derivative B on heart rate in dose of 240 microgram/rat were stronger than nifedipine in times of 15 to 60 minutes after injection (P < 0.05). Conclusion: Novel dihydropyridine derivatives can possess more potent and stable inhibitory effects on systolic blood pressure and heart rate, and some part of these properties at least, can be attributed to their direct inhibitory effects on brain neurons.