Idazoxan effects upon contractile activity in the rat aorta are related to α₁ adrenoceptors and L‐type channels

Abstract

Idazoxan is an alpha(2) adrenoceptor antagonist and alpha(1)/alpha(2) partial agonist which also blocks imidazoline receptors. Although idazoxan is widely used in pharmacological studies, its intrinsic vasoactive properties could bring about some limitations. Others have shown that in rat aorta contracted by phenylephrine idazoxan induces relaxation and that in rat small arteries it preferentially antagonizes the alpha(1)-mediated response. We further investigated this matter, using the rat aorta and focusing on the endothelium-independent effects and on L-type channels. In our study, idazoxan inhibited the contraction induced by phenylephrine, an effect which was stronger in the presence of endothelium, but did not affect the contractions induced by various other agents (high potassium, angiotensin II, prostaglandin F(2alpha)). This preferential inhibition was attenuated by 10(-4) m, but not by 10(-5) m yohimbine, and also reduced by 10(-2) m tetraethylammonium and blunted by 10(-4) m methoxyverapamil. In concentrations above 10(-5) m idazoxan induced weak contractions of the de-endothelized rings, which were prazosin- and methoxyverapamil-sensitive. Others have suggested that cyclic guanosine monophospate mediates the idazoxan-induced endothelium-dependent relaxation, but this is difficult to reconcile with our findings. Potassium efflux could play some role in the direct relaxing effect of idazoxan. The observed idazoxan effects appear as based on action upon alpha(1) receptors, but a direct interaction with L-type calcium channels could also be taken into consideration.

Comparative effects of idazoxan, efaroxan, and BU 224 on insulin secretion in the rabbit: Not only interaction with pancreatic imidazoline I2 binding sites

“…It is also noteworthy that nimodipine similarly abolished the effect of idazoxan and that just simple reduction in the Ca 2+ concentration in the extracellular medium severely attenuated the ligand response. An α-1 partial agonist effect of idazoxan has been recently reported [35]. However there is no evidence for a α-1 adrenoceptor involvement in insulin secretion in isolated islets [36].…”