Antagonism to noradrenaline-induced lethality in rats is related to affinity for the alpha(1A)-adrenoceptor subtype

The potency of several al-adrenoceptor antagonists in preventing the noradrenaline-induced lethality in conscious rats, their binding affinity for the native alpha(1A)- and alpha(1B)-adrenoceptors, the recombinant animal alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptor subtypes, as well as their functional affinity for the alpha 1L-adrenoceptor subtype were evaluated. The potency of the tested compounds as antagonists of noradrenaline-induced lethality was correlated with the affinity for the alpha(1A)- (and alpha(1a)-) adrenoceptor subtype, but not with the affinity for the other subtypes. On the contrary, the hypotensive effects of the compounds, assessed in anesthetized rats, were not clearly related with the affinity for any of the alpha(1)-subtypes. These results suggest that the alpha(1A)-subtype plays a determining role in preventing lethality induced by noradrenaline in the rats, and that this activity is unrelated to the hypotensive effect of the compounds, which cannot be clearly correlated with affinity for a particular alpha(1)-adrenoceptor subtype.