α2‐adrenoceptor ligands inhibit α1‐adrenoceptor‐mediated contraction of isolated rat arteries

AbstractThe experiments in this study were designed to investigate the potential relaxing effects of different compounds known as α2‐imidazoline ligands (either agonists or antagonists) in isolated rat arteries, and to test the role of nitric oxide (NO) and prostaglandins, in addition to the influence of the nature of the contracting agent in these responses. Segments of mesenteric arteries were isolated and mounted in a small vessel myograph (JP Trading, Aarhus, Denmark) for isometric tension recording, while segments of gracilis muscle arteries were cannulated and studied in the pressurized state using an arteriograph (Living Systems Instrumentation, Burlington, VT, USA).In phenylephrine precontracted mesenteric arteries, the agonists clonidine, BHT920, UK 14304, and rilmenidine, as well as the antagonists idazoxan, yohimbine and rauwolscine, all induced marked relaxations. Similarly, clonidine and idazoxan, both induced marked dilatations of phenylephrine preconstricted gracilis muscle arteries. In both mesenteric and gracilis muscle arteries, the responses to clonidine and idazoxan were not affected by the NO synthase inhibitor Nω‐nitro‐L‐arginine (L‐NA, 10−5 M) or the cyclooxygenase inhibitor diclofenac (10−5 M). In mesenteric arteries, the responses to clonidine or idazoxan were similar when the arteries were precontracted by different α1‐adrenoceptor agonists (phenylephrine, methoxamine or norepinephrine). In contrast, in arteries precontracted by PGF2α or endothelin, clonidine induced contractions while idazoxan induced very modest relaxations.Thus, α2‐adrenoceptor/imidazoline ligands (whether agonists and antagonists) induce paradoxical relaxation of small mesenteric or gracilis muscle arteries of rats, which are not affected by NO‐synthase or cyclooxygenase inhibition, and appear related to direct non specific interactions of the α2‐imidazoline ligands with α1‐adrenergic receptors in vascular smooth muscle.