Ageing influences the effect of pre-hypoxic administration of clonidine, an alpha₂-adrenoceptor agonist, on post-hypoxic vasomotricity

In a previous study, we showed that clonidine, an α₂-adrenoceptor agonist, administered prior to hypoxia improves post-hypoxic contractility (PC) and endothelium-dependent dilatation (PED) in isolated young rat aortas. These effects were not investigated in old rats. Ageing influences vascular physiology and modifies the response to vasoactive drugs. Some drugs, such as simvastatin, improve endothelial function, a pivotal component of vascular homeostasis. This study intends to investigate the effect of pre-hypoxic clonidine administration on post-hypoxic vasomotricity in old rats with or without simvastatin. Isolated aortic rings from young and old rats were submitted to hypoxia/reoxygenation (20 min/40 min). For each aorta ring from one rat, clonidine (10⁻⁵ M) was administered in two randomised baths and washed out before hypoxia; two other baths constituted the control group. In some experiments, the old rats were treated with simvastatin (10 mg x kg⁻¹ x day⁻¹) 3 days prior to hypoxia. PED and PC were assessed in all baths. Clonidine enhances PED in young rats (p<0.001) but decreases it in old rats (p=0.038). In young rats, clonidine improves PC (p<0.001), but this effect is not present in old rats (p=0.339). Without endothelium, clonidine does not influence PC in young rats (p= 0.687) but decreases it in old rats (p<0.001). In the simvastatin group, clonidine improves PED (p<0.001) but does not influence PC (p=0.203). In young rats, clonidine increases PED and PC, while it decreases PED and does not influence PC in old rats. With simvastatin, clonidine improves PED but does not influence PC.