The hemodynamic effects of diltiazem (DTZ), losartan, amlodipine and dipyridamole are compared in a rat model following repeated subcutaneous injections. Male SD rats (n = 6 - 14 per group) weighing between 300 - 450 g were used. Each rat received either saline (control) or 5 mg/kg of one of the anti-ischemia agents subcutaneously (s.c.) twice daily (bid) for 5 doses. Hemodynamic measurements were recorded continuously for each animal before and following treatment for up to 6 hours (h). Data were analyzed by ANOVA followed by multiple comparison using the Dunnett’s test and differences considered significance when p < 0.05. The basal SBP, DBP and HR in the control SD rats measured over 6 hours were 131 ± 14 mmHg, 102 ± 17 mmHg, and 460 ± 30 bpm, respectively. While the anti-hypertensive agents (diltiazem, losartan and amlodipine) lowered SBP and DBP rapidly after injection (p < 0.05), the effect on lowering BP measured over the 6 hours compared to the control rats were greatest for amlodipine (SBP -22% and DBP -28%), followed by losartan (SBP -10% and DBP -17%) (p < 0.05 for all the values), and then diltiazem (SBP -2.2% and DBP -4%) (p < 0.05 for DBP). On the other hand, dipyridamole increase SBP significantly (p < 0.05), but not DBP. Compared to control rats
, the HR effect measured over the 6 hours was significantly decreased after amlodipine (-5%) and diltiazem (-6%) (p < 0.05). In contrary, losartan increased HR to 488 ± 25 bpm (+6%) (p < 0.05) and dipyridamole has only a modest effect on HR (+2%). Thus the hemodynamic effects are different qualitatively and quantitatively among the anti-ischemia drugs studied.
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