Biological-Time-Dependent Differences in Effect of Verapamil on Rat Aorta and Influence of Endothelium

Abstract

The biological-time-dependent variation in the vasodilator effect of verapamil on rat thoracic aorta was assessed in both endothelium-intact and denuded 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 different times of the day (1, 5, 9, 13, 17, and 21 hours after lights on; HALO). Verapamil caused concentration-dependent relaxations in both endothelium-intact and denuded aortic rings precontracted with phenylephrine (Phe). In endothelium-intact rings, neither the AUC nor the EC₅₀ values for verapamil exhibited significant biological-time-dependent effects, as determined by one-way analysis of variance (ANOVA). In endothelium-denuded rings, AUC values did vary in a statistically significant manner according to the biological time of study, while the EC₅₀ values did not. Endothelium denudation led to an increase in EC₅₀ values at almost every time point. Statistically significant 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 rings.

Key Words:

• Biological rhythm
• Chronopharmacology
• Endothelium
• Verapamil
• Rat aorta