Evidence for involvement of α 1D ‐adrenoceptors in contraction of femoral resistance arteries using knockout mice

The role of α 1D ‐adrenoceptors in vasoconstrictor responses to noradrenaline in mouse femoral resistance arteries was investigated using wire myography in α 1D ‐adrenoceptor knockout ( α 1D ‐KO) and wild‐type (WT) mice of the same genetic background.α 1D ‐KO mice were 2.5‐fold less sensitive than WTs to exogenous noradrenaline and BMY 7378 was significantly less potent against noradrenaline in α 1D ‐KO mice than in WTs, showing a minor contribution of α 1D ‐adrenoceptors in response to noradrenaline. Prazosin and 5‐methyl‐urapidil were equally effective against noradrenaline in α 1D ‐KO and WT mice. Chloroethylclonidine produced a significantly greater attenuation of the response to noradrenaline in α 1D ‐KO mice than in WTs. Responses to electrical field stimulation (EFS), at 2–20 Hz for 10 s and 0.09 ms pulse width were significantly smaller overall in α 1D ‐KOs than in WTs although no significant differences were seen at the different frequencies. BMY 7378 produced significantly greater inhibition of responses at 2 and 5 Hz than at higher frequencies in WTs. In α 1D ‐KOs, this greater sensitivity to BMY 7378 at lower frequencies was not apparent, confirming that the effect of BMY 7378 was due to blockade of α 1D ‐adrenoceptors. Prazosin and 5‐methyl‐urapidil had similar inhibitory effects on responses to EFS in α 1D ‐KO and WT mice. Chloroethylclonidine inhibited responses to EFS to a significantly greater extent in α 1D ‐KO mice. The present study with α 1D ‐KO mice shows that α 1D ‐adrenoceptors contribute to vasoconstrictor responses to exogenous and neurally released noradrenaline in femoral resistance arteries.British Journal of Pharmacology (2005) 146 , 942–951. doi: 10.1038/sj.bjp.0706395