Biological-time-dependent differences in effect of verapamil on rat aorta and influence of endothelium

The biological-time-dependent variation in the vasodilator effect of verapa mil on rat thoracic aorta was assessed in both endothelium-intact and denud ed preparations. Groups of adult male rats were housed in light from; 08:00 :to 20:00 and in darkness from 20:00 to 08:00 and sacrificed at six differe nt times of the day (1, 5, 9, 13, 17, and 21 hours after lights on; HALO). Verapamil caused concentration-dependent relaxations in both endothelium-in tact and denuded aortic rings precontracted with phenylephrine (Phe). In en dothelium-intact rings, neither the AUC nor: the EC50 values for verapamil exhibited significant biological-time-dependent effects as determined by on e-way analysis of variance (ANOVA). In endothelium-denuded rings, AUC value s did vary in a statistically significant manner according to the biologica l time of study, while the EC50 values did not. Endothelium denudation led to an increase in EC50 values at almost every time: point, Statistically si gnificant interactions between the biological time of study and treatment ( intact vs. denuded endothelium) in both AUC and EC50 values were:documented by two-way ANOVA; this indicated. differences in the clock-time staging of verapamil-induced relaxation in endothelium-denuded versus intact aortic r ings.