Clonidine induces rat aorta relaxation by nitric oxide-dependent and -independent mechanisms

The alpha1- and alpha2-adrenoceptors coexist in vascular smooth muscle cells producing vascular contraction and relaxation. This study was designed to investigate which is the mechanism activated by clonidine in the rat aorta, and the endothelial factors possibly involved in the relaxation induced by clonidine. The alpha2-adrenoceptors agonist clonidine relaxed rat aortas pre-contracted with phenylephrine, with or without endothelium. In non-contracted denuded arteries, clonidine produced contractions instead of relaxation. In intact endothelium aortic rings, clonidine induced greater relaxation than in denuded aortic rings. In aortas with intact endothelium, the NO-synthase inhibitor L-NAME (10 micromol/L) and the NO-scavenger hemoglobin (10 micromol/L) reduced the relaxation to clonidine. On the other hand, indomethacin (10 micromol/L) failed to alter the relaxation induced by clonidine. These results suggest the participation of NO, but not prostacyclin in clonidine-induced relaxation. In aortic rings pre-contracted with KCl (60 mmol/L) the relaxation induced by clonidine was abolished; however, the K+ channel blockers glibenclamide (K(ATP)), tetraethylamonium (K(Ca)), and the combination of apamin and charybdotoxin (K(Ca)) did not change the relaxation induced by clonidine. The relaxation induced by clonidine on PGF2alpha-contracted arteries was not affected by prazosin. However, in the absence of prazosin, clonidine had an additional contractile effect in PGF2alpha-contracted arteries. In conclusion, our results show that in rat aorta clonidine can activate alpha2-adrenoceptors in the smooth muscle cells and alpha2-adrenoceptors in the endothelial cells that activates NO production, but not prostacyclin and/or EDHF. In the absence of phenylephrine and prazosin, clonidine can also activate alpha1-adrenoceptors and rat aorta contraction.